%0 Journal Article
%~ PubMed
%A Hafezi, Wali
%A Lorentzen, Eva U
%A Eing, Bodo R
%A Müller, Marcus
%A King, Nicholas J C
%A Klupp, Barbara
%A Mettenleiter, Thomas C
%A Kühn, Joachim E
%T Entry of herpes simplex virus type 1 (HSV-1) into the distal axons of trigeminal neurons favors the onset of nonproductive, silent infection.
%B PLoS Pathogens
%D 2012
%C United States
%I Public Library of Science
%V 8
%N 5
%P e1002679
%@ 1553-7374
%X 
%Z FOR Codes: 110902 110904 110804


%0 Journal Article
%~ PubMed
%A Yeung, Amanda W S
%A Wu, Wei
%A Freewan, Mohammed
%A Stocker, Roland
%A King, Nicholas J C
%A Thomas, Shane R
%T Flavivirus infection induces indoleamine 2,3-dioxygenase in human monocyte-derived macrophages via tumor necrosis factor and NF-κB.
%B Journal of Leukocyte Biology
%D 2012
%C United States
%I Federation of American Societies for Experimental
%V 91
%N 4
%P 657-666
%@ 1938-3673
%X Infection with West Nile virus (WNV) via a mosquito bite results in local viral replication in the skin, followed by viremia. Thus, tissue macrophages are ideally located to prevent the dissemination of WNV throughout the host. The current study shows that WNV infection of human monocyte-derived macrophages (MDM) results in increased WNV mRNA, protein, and infectious virions at 24 h p.i. with a decline in titer after 48 h. Concomitant with viral control was the robust induction of indoleamine 2,3-dioxygenase (IDO) and resultant metabolism of L-tryptophan (L-Trp) to kynurenine. In WNV-exposed cultures, IDO protein was induced primarily in noninfected versus viral-infected MDM. Whereas WNV infection increased the production of IFN-?, IFN-?, and TNF, only antibody neutralization of TNF attenuated IDO expression and activity. WNV infection also activated NF-?B, and inhibition of this pathway with BMS-345541 abrogated IDO induction. Similar results were also obtained with MDM infected with the related flavivirus, Japanese encephalitis virus. Whereas IDO-mediated L-Trp metabolism can exhibit antiviral properties, inhibition of IDO activity in MDM with L-1-MT or the addition of excess L-Trp did not affect viral control. However, culturing MDM in L-Trp-deficient medium or overexpression of IDO in cells prior to infection significantly attenuated WNV replication, which was reversed by adding excess L-Trp. Together, these data support that although IDO is not required by MDM for the clearance of established viral infection, the spread of flavivirus infection is limited by IDO expressed in uninfected, neighboring cells.
%Z FOR Codes: 110707 60506 110804


%0 Journal Article
%~ PubMed
%A Minten, Carsten
%A Terry, Rachael
%A Deffrasnes, Celine
%A King, Nicholas J C
%A Campbell, Iain L
%T IFN regulatory factor 8 is a key constitutive determinant of the morphological and molecular properties of microglia in the CNS.
%B PloS One
%D 2012
%C United States
%I Public Library of Science
%V 7
%N 11
%P e49851
%@ 1932-6203
%X 
%Z FOR Codes: 110904 60111 110799


%0 Journal Article
%~ PubMed
%A Xiang, Xiaogang
%A Gui, Honglian
%A King, Nicholas Jc
%A Cole, Louise
%A Wang, Hui
%A Xie, Qing
%A Bao, Shisan
%T IL-22 and non-ELR-CXC chemokine expression in chronic hepatitis B virus-infected liver.
%B Immunology and Cell Biology
%D 2012
%C United Kingdom, Australia
%I Nature Publishing Group
%V 90
%N 6
%P 611-619
%@ 0818-9641
%X Hepatitis B virus infection is still a major global health problem, despite decades of research. Interleukin (IL)-22 induces acute phase reactants and chemokines, favors anti-microbial defence and protects tissues from damage. IL-22 is important in chronic skin inflammation, but its role in chronic hepatitis B (CHB) is unclear. This study explores the association between intra-hepatic IL-22 expression, its relevant associated cytokines and the severity of liver inflammation/fibrosis in CHB patients. IL-22, IL-17, IL-10, IL-6, non-ELR-CXC chemokines (CXCL-9, CXCL-10, CXCL-11), fibroblast growth factors and Kupffer cell (KC) numbers were measured in patients with CHB (n=65), acute hepatitis B (AHB; n=4), chronic hepatitis C (CHC; n=14) and non-viral hepatitis (n=23), using immunohistochemistry. Expression of IL-22, IL-17, IL-10, IL-6, non-ELR-CXC chemokines and number of KCs in liver tissues were substantially higher in AHB patients than others. In CHB patients, the expression of IL-22, IL-6, CXCL-9 and CXCL-10 were significantly higher with alanine aminotransferase (ALT) levels ???twice the upper limit of normal (ULN), compared with those with ALT levels >twice the ULN, whereas IL-10 and IL-17 showed a reverse pattern. IL-22 was inversely (P<0.01), but IL-17 was positively (P<0.05), correlated with the histological activity index) in these patients, and a significant negative correlation between the fibrosis stage and IL-22 or non-ELR-CXC chemokines was observed. Furthermore, immunofluorescent labeling demonstrated a close spatial association of IL-22, CXCL-9, -10 or -11 in the CHB liver. We speculate that IL-22 and non-ELR-CXC chemokines synergistically may provide protection in liver inflammation/fibrosis during CHB infection.Immunology and Cell Biology advance online publication, 27 September 2011; doi:10.1038/icb.2011.79.
%Z FOR Codes: 110704 110804 1107


%0 Journal Article
%~ PubMed
%A Terry, Rachael L
%A Getts, Daniel R
%A Deffrasnes, Celine
%A van Vreden, Caryn
%A Campbell, Iain L
%A King, Nicholas Jc
%T Inflammatory monocytes and the pathogenesis of viral encephalitis.
%B Journal of Neuroinflammation
%D 2012
%C United Kingdom
%I BioMed Central Ltd.
%V 9
%N 
%P 270
%@ 1742-2094
%X 
%Z FOR Codes: 110902 110707


%0 Journal Article
%~ PubMed
%A Hofer, Markus J
%A Li, Wen
%A Manders, Peter
%A Terry, Rachael
%A Lim, Sue Ling
%A King, Nicholas J C
%A Campbell, Iain L
%T Mice deficient in STAT1 but not STAT2 or IRF9 develop a lethal CD4+ T-cell-mediated disease following infection with lymphocytic choriomeningitis virus.
%B Journal of Virology
%D 2012
%C United States
%I American Society for Microbiology
%V 86
%N 12
%P 6932-6946
%@ 1098-5514
%X Interferon (IFN) signaling is crucial for antiviral immunity. While Type I IFN signaling is mediated by STAT1, STAT2 and IRF9, type II IFN signaling requires only STAT1. Here, we studied the role of these signaling factors in the host response to systemic infection with Lymphocytic choriomeningitis virus (LCMV). In wild type (WT) mice and mice lacking either STAT2 or IRF9, LCMV infection was non-lethal and the virus was either cleared (WT) or established persistence (STAT2 KO and IRF9 KO). However, in the case of STAT1 KO mice, LCMV infection was lethal and accompanied by severe multi-organ immune pathology, elevated expression of various cytokine genes in tissues, and cytokines in the serum. This lethal phenotype was unaltered by the co-absence of the IFN-? receptor and hence was not dependent on IFN-?. Equally, this disease was not due to a combined defect in type I and type II IFN signaling as IRF9 mice lacking the IFN-? receptor survived infection with LCMV. Clearance of LCMV is mediated normally by CD8(+) T-cells. However, the depletion of these cells in LCMV-infected STAT1 KO mice delayed, but did not prevent, lethality. By contrast, depletion of CD4(+) T-cells prevented lethality in LCMV-infected STAT1 KO mice and was associated with a reduction in tissue immune pathology. These studies highlight a fundamental difference in the role of STAT1 versus STAT2 and IRF9. While all three factors limit viral replication and spread, only STAT1 has the unique function to prevent the emergence of a lethal antiviral CD4(+) T-cell response.
%Z FOR Codes: 110903 110704


%0 Journal Article
%~ PubMed
%A Munoz-Erazo, Luis
%A Natoli, Ricardo
%A Provis, Jan Marie
%A Madigan, Michelle Catherine
%A King, Nicholas Jonathan Cole
%T Microarray analysis of gene expression in West Nile virus-infected human retinal pigment epithelium.
%B Molecular Vision
%D 2012
%C United States
%I Molecular Vision
%V 18
%N 
%P 730-743
%@ 1090-0535
%X To identify key genes differentially expressed in the human retinal pigment epithelium (hRPE) following low-level West Nile virus (WNV) infection.
%Z FOR Codes: 60506 110707 110704


%0 Journal Article
%~ PubMed
%A Getts, Daniel R
%A Martin, Aaron J
%A McCarthy, Derrick P
%A Terry, Rachael L
%A Hunter, Zoe N
%A Yap, Woon Teck
%A Getts, Meghann Teague
%A Pleiss, Michael
%A Luo, Xunrong
%A King, Nicholas Jc
%A Shea, Lonnie D
%A Miller, Stephen D
%T Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis.
%B Nature Biotechnology
%D 2012
%C United States
%I Nature Publishing Group
%V 30
%N 
%P 1217-1224
%@ 1546-1696
%X 
%Z FOR Codes: 110703 110904 110707


%0 Journal Article
%~ PubMed
%A Getts, Daniel R
%A Terry, Rachael L
%A Getts, Meghann Teague
%A Müller, Marcus
%A Rana, Sabita
%A Deffrasnes, Celine
%A Ashhurst, Thomas Myles
%A Radford, Jane
%A Hofer, Markus
%A Thomas, Shane
%A Campbell, Iain L
%A King, Nicholas Jc
%T Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA)-4-dependent recruitment of nitric oxide-producing macrophages.
%B Journal of Neuroinflammation
%D 2012
%C United Kingdom
%I BioMed Central Ltd.
%V 9
%N 1
%P 246
%@ 1742-2094
%X 
%Z FOR Codes: 110704


%0 Journal Article
%~ PubMed
%A Davison, Ariane M
%A King, Nicholas J C
%T Accelerated dendritic cell differentiation from migrating Ly6C(lo) bone marrow monocytes in early dermal West Nile virus infection.
%B Journal of Immunology
%D 2011
%C United States
%I American Association of Immunologists
%V 186
%N 4
%P 2382-2396
%@ 1550-6606
%X No study has investigated the participation of Ly6C(+) monocytes in the earliest phase of skin infection with the mosquito-borne West Nile virus. In a novel murine model mimicking natural dermal infection, CCL2-dependent bone marrow (BM)-derived monocyte migration, differentiation into Ly6C(+) dendritic cells (DC), and accumulation around dermal deposits of infected fibroblasts by day 1 postinfection were associated with increasing numbers of monocyte-derived TNF/inducible NO synthase-producing DC by day 2 postinfection in draining auricular lymph nodes (ALN). Adoptive transfer demonstrated simultaneous migration of bone marrow-derived Ly6C(lo) monocytes to virus-infected dermis and ALN, where they first become Ly6C(hi) DC within 24 h and then Ly6C(lo) DC by 72 h. DC migration from the infected dermis to the ALN derived exclusively from Ly6C(lo) BM monocytes. This demonstrates that Ly6C(hi) and Ly6C(lo) BM-derived monocytes have different fates in vivo and suggests that BM may be a reservoir of preinflammatory monocytes for rapid deployment as inflammatory DC during virus infection.
%Z FOR Codes: 110707


%0 Journal Article
%~ PubMed
%A Van Ly, David
%A King, Nicholas J C
%A Moir, Lyn M
%A Burgess, Janette K
%A Black, Judith L
%A Oliver, Brian G
%T Effects of &#946;(2) Agonists, Corticosteroids, and Novel Therapies on Rhinovirus-Induced Cytokine Release and Rhinovirus Replication in Primary Airway Fibroblasts.
%B Journal of Allergy
%D 2011
%C United States
%I Hindawi Publishing Corporation
%V 2011
%N 
%P 457169
%@ 1687-9791
%X Rhinovirus-(RV-) induced asthma exacerbations account for high asthma-related health costs and morbidity in Australia. The cellular mechanism underlying this pathology is likely the result of RV-induced nuclear-factor-kappa-B-(NF-?B-) dependent inflammation. NF-?B may also be important in RV replication as inhibition of NF-?B inhibits replication of other viruses such as human immunodeficiency virus and cytomegalovirus. To establish the role of NF-?B inhibitors in RV-induced IL- 6 and IL-8 and RV replication, we used pharmacological inhibitors of NF-?B, and steroids and/or ?(2) agonists were used for comparison. Primary human lung fibroblasts were infected with RV-16 in the presence of NF-?B inhibitors: BAY-117085 and dimethyl fumarate; ?(2) agonist: salmeterol; and/or corticosteroids: dexamethasone; fluticasone. RV-induced IL-6 and IL-8 and RV replication were assessed using ELISAs and virus titration assays. RV replicated and increased IL-6 and IL-8 release. Salmeterol increased, while dexamethasone and fluticasone decreased RV-induced IL-6 and IL-8 (P<0.05). The NF-?B inhibitor BAY-117085 inhibited only RV-induced IL-6 (P<0.05) and dimethyl fumarate did not alter RV-induced IL-6 and IL-8. Dimethylfumarate increased RV replication whilst other drugs did not alter RV replication. These data suggest that inhibition of NF-?B alone is unlikely to be an effective treatment compared to current asthma therapeutics.
%Z FOR Codes: 602


%0 Journal Article
%A Say, Jana M
%A van Vreden, Caryn
%A Reilly, David J.
%A Brown, Louise J.
%A Rabeau, James R.
%A King, Nicholas
%T Luminescent nanodiamonds for biomedical applications
%B Biophysical Reviews
%D 2011
%C Germany
%I Springer
%V 3
%N 4
%P 171-184
%@ 1867-2450
%X 
%Z FOR Codes: 100499


%0 Journal Article
%~ PubMed
%A Ling, Zheng Lung
%A Combes, Valery
%A Grau, Georges E
%A King, Nicholas J C
%T Microparticles as immune regulators in infectious disease - an opinion.
%B Frontiers in Immunology
%D 2011
%C Switzerland
%I Frontiers Research Foundation
%V 2
%N 
%P 67
%@ 1664-3224
%X Despite their clear relationship to immunology, few existing studies have examined the potential role of microparticles (MP) in infectious disease. MP have a different size range from exosomes and apoptotic bodies, with which they are often grouped and arise by different mechanisms in association with inflammatory cytokine action or stress on the source cell. Infection with pathogens usually leads to the expression of a range of inflammatory cytokines and chemokines, as well as significant stress in both infected and uninfected cells. It is thus reasonable to infer that infection-associated inflammation also leads to MP production. MP are produced by most of the major cell types in the immune system, and appear to be involved at both innate and adaptive levels, potentially serving different functions in each. Thus, they do not appear to have a universal function; instead their functions are source- or stimulus-dependent, although likely to be primarily either pro- or anti-inflammatory. We argue that in infectious diseases, MP may be able to deliver antigen, derived from the biological cargo acquired from their cells of origin, to antigen-presenting cells. Another potential benefit of MP would be to transfer and/or disseminate phenotype and function to target cells. However, MP may also potentially be manipulated, particularly by intracellular pathogens, for survival advantage.
%Z FOR Codes: 110704


%0 Journal Article
%~ PubMed
%A Kuo, Curtis
%A Lim, Sam
%A King, Nicholas J C
%A Bartlett, Nathan W
%A Walton, Ross P
%A Zhu, Jie
%A Glanville, Nicholas
%A Aniscenko, Julia
%A Johnston, Sebastian L
%A Burgess, Janette K
%A Black, Judith L
%A Oliver, Brian G
%T Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo.
%B Respirology
%D 2011
%C Australia, Japan
%I Wiley-Blackwell Publishing Asia
%V 16
%N 2
%P 367-377
%@ 1440-1843
%X A hallmark of asthma is airway remodelling, which includes increased deposition of extracellular matrix (ECM) protein. Viral infections may promote the development of asthma and are the most common causes of asthma exacerbations. We evaluated whether rhinovirus (RV) infection induces airway remodelling, as assessed by ECM deposition.
%Z FOR Codes: 60106


%0 Journal Article
%~ PubMed
%A Kuo, Curtis
%A Lim, Sam
%A King, Nicholas J C
%A Johnston, Sebastian L
%A Burgess, Janette K
%A Black, Judith L
%A Oliver, Brian G
%T Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and non-asthmatic airway smooth muscle cells.
%B American Journal of Physiology: Lung Cellular and Molecular Physiology
%D 2011
%C United States
%I American Physiological Society
%V 300
%N 6
%P L951-L957
%@ 1522-1504
%X Airway remodeling, which includes increases in the extracellular matrix (ECM), is a characteristic feature of asthma and is correlated to disease severity. Rhinovirus (RV) infections are associated with increased risk of asthma development in young children and are the most common cause of asthma exacerbations. We examined whether viral infections can increase ECM deposition and whether this increased ECM modulates cell proliferation and migration. RV infection of nonasthmatic airway smooth muscle (ASM) cells significantly increased the deposition of fibronectin (40% increase, n = 12) and perlecan (80% increase, n = 14), while infection of asthmatic ASM cells significantly increased fibronectin (75% increase, n = 9) and collagen IV (15% increase, n = 9). We then treated the ASM cells with the Toll-like receptor (TLR) agonists polyinosinic:polycytidylic acid, imiquimod, and pure RV RNA and were able to show that the mechanism through which RV induced ECM deposition was via the activation of TLR3 and TLR7/8. Finally, we assessed whether the virus-induced ECM was bioactive by measuring the amount of migration and proliferation of virus-naive cells that seeded onto the ECM. Basically, ECM from asthmatic ASM cells induced twofold greater migration of virus-naive ASM cells than ECM from nonasthmatic ASM cells, and these rates of migration were further increased on RV-modulated ECM. Increased migration on the RV-modulated ECM was not due to increased cell proliferation, as RV-modulated ECM decreased the proliferation of virus-naive cells. Our results suggest that viruses may contribute to airway remodeling through increased ECM deposition, which in turn may contribute to increased ASM mass via increased cell migration.
%Z FOR Codes: 111501 60506


%0 Book Section
%A King, Nicholas
%A Van Vreden, Caryn
%A Terry, Rachael L
%A Getts, Daniel R
%A Yeung, Amanda WS
%A M, Teague-Getts
%A Ariane M, Davison
%A Deffrasnes, Celine
%A Luis, Munoz-Erazo
%T The Immunopathogenesis of Neurotropic Flavivirus Infection
%B Flavivirus Encephalitis
%D 2011
%C Croatia
%I InTech
%V 
%N 
%P 25-52
%@ 9789533076690
%E R&#367;žek, Daniel
%X 
%Z FOR Codes: 60502


%0 Journal Article
%~ PubMed
%A Getts, Daniel R
%A Turley, Danielle M
%A Smith, Cassandra E
%A Harp, Christopher T
%A McCarthy, Derrick
%A Feeney, Emma M
%A Getts, Meghann Teague
%A Martin, Aaron J
%A Luo, Xunrong
%A Terry, Rachael L
%A King, Nicholas J C
%A Miller, Stephen D
%T Tolerance Induced by Apoptotic Antigen-Coupled Leukocytes Is Induced by PD-L1+ and IL-10-Producing Splenic Macrophages and Maintained by T Regulatory Cells.
%B Journal of Immunology
%D 2011
%C United States
%I American Association of Immunologists
%V 187
%N 5
%P 2405-2417
%@ 1550-6606
%X Ag-specific tolerance is a highly desired therapy for immune-mediated diseases. Intravenous infusion of protein/peptide Ags linked to syngeneic splenic leukocytes with ethylene carbodiimide (Ag-coupled splenocytes [Ag-SP]) has been demonstrated to be a highly efficient method for inducing peripheral, Ag-specific T cell tolerance for treatment of autoimmune disease. However, little is understood about the mechanisms underlying this therapy. In this study, we show that apoptotic Ag-SP accumulate in the splenic marginal zone, where their uptake by F4/80(+) macrophages induces production of IL-10, which upregulates the expression of the immunomodulatory costimulatory molecule PD-L1 that is essential for Ag-SP tolerance induction. Ag-SP infusion also induces T regulatory cells that are dispensable for tolerance induction but required for long-term tolerance maintenance. Collectively, these results indicate that Ag-SP tolerance recapitulates how tolerance is normally maintained in the hematopoietic compartment and highlight the interplay between the innate and adaptive immune systems in the induction of Ag-SP tolerance. To our knowledge, we show for the first time that tolerance results from the synergistic effects of two distinct mechanisms, PD-L1-dependent T cell-intrinsic unresponsiveness and the activation of T regulatory cells. These findings are particularly relevant as this tolerance protocol is currently being tested in a Phase I/IIa clinical trial in new-onset relapsing-remitting multiple sclerosis.
%Z FOR Codes: 110704 110707


%0 Journal Article
%~ PubMed
%A Trian, Thomas
%A Ge, Qi
%A Moir, Lyn M
%A Burgess, Janette K
%A Kuo, Curtis
%A King, Nicholas J C
%A Reddel, Helen K
%A Black, Judith L
%A Oliver, Brian G
%A McParland, Brent E
%T Rhinovirus-induced Exacerbations of Asthma - How is the {beta}2-adrenoceptor Implicated?
%B American journal of respiratory cell and molecular biology
%D 2010
%C United States
%I American Thoracic Society
%V 43
%N 2
%P 227-33
%@ 1535-4989
%X Rhinovirus (RV) infections are the major cause of asthma exacerbations in children and adults. Under normal circumstances, asthmatic airway obstruction improves spontaneously or characteristically briskly in response to inhaled beta(2)-adrenergic receptor (beta(2)AR) agonists. During virus-associated exacerbations, an impaired response to beta(2)AR agonists is observed; the reason for this is not known. The objective of this study was to determine the effect of RV infection on airway smooth muscle beta(2)AR function. The human cell line Beas-2B and primary human bronchial epithelial cells (HBECs) were infected with RV (multiplicity of infection = 1). After 1 or 5 days for primary and Beas-2B cells, respectively, cell culture supernatants were harvested, UV-irradiated to inactivate RV, and applied to human airway smooth muscle cells for 3 days to assess modifications of beta(2)AR function. RV conditioned medium from Beas-2B and HBECs decreased beta(2)AR agonist-induced cAMP by 50 and 65%, respectively (n = 5; P < 0.05). When cAMP was induced independently of the beta(2)AR using forskolin, no impairment was found. Using flow cytometry, we demonstrated that this decrease was likely the result of beta(2)AR desensitization because membrane but not total cell receptor beta(2)AR was decreased. Pretreatment of HBECs and Beas-2B cells but not human airway smooth muscle cells with the corticosteroids dexamethasone or fluticasone abolished virus-mediated beta(2)AR loss of function. This study shows that epithelial infection with RV induces a decrease of beta(2)AR function on airway smooth muscle cells, potentially explaining the clinical observation of loss of beta(2)AR agonist function during RV-induced asthma exacerbations.
%Z FOR Codes: 111501 110804 111601 110106


%0 Journal Article
%~ PubMed
%A Kashem, Mohammed A
%A Sarker, Ranjana
%A Des Etages, H
%A Machaalani, Rita
%A King, Nicholas
%A McGregor, Iain S
%A Matsumoto, Izuru
%T Comparative proteomics in the corpus callosal sub-regions of postmortem human brain.
%B Neurochemistry international
%D 2009
%C United Kingdom
%I Elsevier Ltd
%V 55
%N 7
%P 483-90
%@ 0197-0186
%X The corpus callosum (CC) is a single anatomical region with homologous cytoarchitecture and divided into four sub-regions such as the rostrum, the genu, the body and the splenium. Neuroimaging analysis revealed that susceptibility to clinical neurological diseases of these sub-regions is variable, indicating biochemical and physiological heterogenecity. To understand the biochemical make up of these regions, we compared the protein expression of these three sub-regional areas [the genu, the body and the splenium (n=9)] through 2D proteomics, which is a high-throughput global protein expression analysis technique. Normative proteomic comparison of gels, and analysis of spectra revealed that 17 (identified as 7 proteins), 35 (identified as 20 proteins) and 39 (identified as 21 proteins) protein spots were differentially expressed in the genu vs. the body, the genu vs. the splenium and the body vs. the splenium, respectively. These results suggest that the sub-regions of the CC differ at the level of protein expression. Identified proteins of the different groups belong to several functional classes such as cytoskeletal, metabolic, signaling, oxidative stress and calcium regulation. Interestingly, oxidative stress defense and glucose metabolic pathways of the splenium are quite different from the genu which might be correlated to region specific vulnerability of neuronal illness. Protein expression maps of these regions can be used as a reference source for future studies to investigate the molecular basis of functional differences and degree of pathogenesis of various neurodegenerative diseases of the CC.
%Z FOR Codes: 110903 30406 110106


%0 Book Section
%A King, Nicholas
%A Davison, Ariane
%A Getts, Daniel R
%A Lu, David Ping
%A Getts, Meghann Teague
%A Yeung, Amanda
%A Peterson, James K
%A Kesson, Alison M
%T Enhanced Antigen Processing or Immune Evasion? West Nile Virus and the Induction of Immune Recognition Molecules
%B West Nile Encephalitis Virus Infection
%D 2009
%C United States
%I Springer
%V 
%N 
%P 309-339
%@ 9780387798394
%E Diamond, Michael S
%X 
%Z FOR Codes: 110701 110309


%0 Journal Article
%~ PubMed
%A Quintana, Albert
%A Müller, Marcus
%A Frausto, Ricardo F
%A Ramos, Raquel
%A Getts, Daniel R
%A Sanz, Elisenda
%A Hofer, Markus J
%A Krauthausen, Marius
%A King, Nicholas J C
%A Hidalgo, Juan
%A Campbell, Iain L
%T Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis.
%B Journal of Immunology
%D 2009
%C United States
%I American Association of Immunologists
%V 183
%N 3
%P 2079-2088
%@ 0022-1767
%X IL-6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. To establish the role of site-specific production of IL-6 in autoimmunity, we examined myelin oligodendrocyte glycoprotein immunization-induced EAE in transgenic mice (GFAP-IL6) with IL-6 production restricted to the cerebellum. Myelin oligodendrocyte glycoprotein-immunized (Mi-) GFAP-IL6 mice developed severe ataxia but no physical signs of spinal cord involvement, which was in sharp contrast to Mi-wild type (WT) animals that developed classical EAE with ascending paralysis. Immune pathology and demyelination were nearly absent from the spinal cord, but significantly increased in the cerebellum of Mi-GFAP-IL6 mice. Tissue damage in the cerebellum in the Mi-GFAP-IL6 mice was accompanied by increased total numbers of infiltrating leukocytes and increased proportions of both neutrophils and B-cells. With the exception of IL-17 mRNA, which was elevated in both control immunized and Mi-GFAP-IL6 cerebellum, the level of other cytokine and chemokine mRNAs were comparable with Mi-WT cerebellum whereas significantly higher levels of IFN-gamma and TNF-alpha mRNA were found in Mi-WT spinal cord. Thus, site-specific production of IL-6 in the cerebellum redirects trafficking away from the normally preferred antigenic site the spinal cord and acts as a leukocyte "sink" that markedly enhances the inflammatory cell accumulation and disease. The mechanisms underlying this process likely include the induction of specific chemokines, activation of microglia, and activation and loss of integrity of the blood-brain barrier present in the cerebellum of the GFAP-IL6 mice before the induction of EAE.
%Z FOR Codes: 110704 110903


%0 Journal Article
%~ PubMed
%A Patel, Manish I
%A Singh, Jaskirat
%A Niknami, Marzieh
%A Kurek, Caroline
%A Yao, Mu
%A Lu, Sasa
%A Maclean, Fiona
%A King, Nicholas J C
%A Gelb, Michael H
%A Scott, Kieran F
%A Russell, Pamela J
%A Boulas, John
%A Dong, Qihan
%T Cytosolic Phospholipase A2-{alpha}: A Potential Therapeutic Target for Prostate Cancer.
%B Clinical Cancer Research
%D 2008
%C United States
%I American Association for Cancer Research
%V 14
%N 24
%P 8070-8079
%@ 1078-0432
%X PURPOSE: Cytosolic phospholipase A2-alpha (cPLA(2)-alpha) provides intracellular arachidonic acid to supply both cyclooxygenase and lipoxygenase pathways. We aim to determine the expression and activation of cPLA(2)-alpha in prostate cancer cell lines and tissue and the effect of targeting cPLA(2)-alpha in vitro and in vivo. EXPERIMENTAL DESIGN: The expression of cPLA(2)-alpha was determined in prostate cancer cells by reverse transcription-PCR, Western blot, and immunocytochemistry. Growth inhibition, apoptosis, and cPLA(2)-alpha activity were determined after inhibition with cPLA(2)-alpha small interfering RNA or inhibitor (Wyeth-1). Cytosolic PLA(2)-alpha inhibitor or vehicle was also administered to prostate cancer xenograft mouse models. Finally, the expression of phosphorylated cPLA(2)-alpha was determined by immunohistochemistry in human normal, androgen-sensitive and androgen-insensitive prostate cancer specimens. RESULTS: cPLA(2)-alpha is present in all prostate cancer cells lines, but increased in androgen-insensitive cells. Inhibition with small interfering RNA or Wyeth-1 results in significant reductions in prostate cancer cell numbers, as a result of reduced proliferation as well as increased apoptosis, and this was also associated with a reduction in cPLA(2)-alpha activity. Expression of cyclin D1 and phosphorylation of Akt were also observed to decrease. Wyeth-1 inhibited PC3 xenograft growth by approximately 33% and again, also reduced cyclin D1. Immunohistochemistry of human prostate tissue revealed that phosphorylated cPLA(2)-alpha is increased when hormone refractory is reached. CONCLUSIONS: Expression and activation of cPLA(2)-alpha are increased in the androgen-insensitive cancer cell line and tissue. Inhibition of cPLA(2)-alpha results in cells and xenograft tumor growth inhibition and serves as a potentially effective therapy for hormone refractory prostate cancer.
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Getts, Daniel R
%A Terry, Rachael L
%A Getts, Meghann Teague
%A Müller, Marcus
%A Rana, Sabita
%A Shrestha, Bimmi
%A Radford, Jane
%A Van Rooijen, Nico
%A Campbell, Iain L
%A King, Nicholas J C
%T Ly6c+ "inflammatory monocytes" are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis.
%B The Journal of experimental medicine
%D 2008
%C United States
%I Rockefeller University Press
%V 205
%N 0
%P 2319-37
%@ 1540-9538
%X In a lethal West Nile virus (WNV) model, central nervous system infection triggered a threefold increase in CD45(int)/CD11b(+)/CD11c(-) microglia at days 6-7 postinfection (p.i.). Few microglia were proliferating, suggesting that the increased numbers were derived from a migratory precursor cell. Depletion of "circulating" (Gr1(-)(Ly6C(lo))CX3CR1(+)) and "inflammatory" (Gr1(hi)/Ly6C(hi)/CCR2(+)) classical monocytes during infection abrogated the increase in microglia. C57BL/6 chimeras reconstituted with cFMS-enhanced green fluorescent protein (EGFP) bone marrow (BM) showed large numbers of peripherally derived (GFP(+)) microglia expressing GR1(+)(Ly6C(+)) at day 7 p.i., suggesting that the inflammatory monocyte is a microglial precursor. This was confirmed by adoptive transfer of labeled BM (Ly6C(hi)/CD115(+)) or circulating inflammatory monocytes that trafficked to the WNV-infected brain and expressed a microglial phenotype. CCL2 is a chemokine that is highly expressed during WNV infection and important in inflammatory monocyte trafficking. Neutralization of CCL2 not only reduced the number of GFP(+) microglia in the brain during WNV infection but prolonged the life of infected animals. Therefore, CCL2-dependent inflammatory monocyte migration is critical for increases in microglia during WNV infection and may also play a pathogenic role during WNV encephalitis.
%Z FOR Codes: 110799


%0 Journal Article
%~ PubMed
%A Oliver, Brian G
%A Lim, Sam
%A Wark, Peter
%A Laza-Stanca, Vasile
%A King, Nicholas J C
%A Black, Judith L
%A Burgess, Janette K
%A Roth, Michael
%A Johnston, Sebastian L
%T Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages.
%B Thorax
%D 2008
%C London
%I British Medical Journal Publishing Group
%V 63
%N 6
%P 519-25
%@ 1468-3296
%X Rhinovirus infection is responsible for considerable morbidity and mortality as the major cause of exacerbations of asthma, and is also known to induce exacerbations of cystic fibrosis and chronic obstructive pulmonary disease. Exacerbations of these diseases are also frequently associated with bacterial and atypical bacterial infection. Alveolar macrophages are the major immune cells in the airways and are important in defence against bacterial infections.
%Z FOR Codes: 110804


%0 Journal Article
%~ PubMed
%A Getts, Daniel R
%A Balcar, Vladimir J
%A Matsumoto, Izuru
%A Müller, Marcus
%A King, Nicholas J C
%T Viruses and the immune system: their roles in seizure cascade development.
%B Journal of neurochemistry
%D 2008
%C UK
%I Blackwell Publishing Ltd
%V 104
%N 5
%P 1167-1176
%@ 1471-4159
%X Viral encephalitis affects approximately 7.5 people/100 000 and carries a high rate of morbidity and mortality. Most patients with viral encephalitis will develop some form of seizure during the infectious process, and of those who survive encephalitic disease, approximately 4-20% will develop epilepsy. Arthropod-borne (arbo)viruses are the leading cause of viral encephalitis in the world today, with between 10% and 35% of patients infected with these viruses displaying some form of seizure. Several neurotropic DNA viruses, including Herpes and cytomegalovirus also commonly cause seizures in infected patients. In the clinical setting, the cause of seizures seen during viral encephalitis is usually attributed to acute febrile responses. However, it has become apparent that the mechanisms behind seizure generation during viral encephalitis are likely to be much more complicated. For example, CD4(+) and CD8(+) T cells possibly through their secretion of interferon-gamma, appear to play an important role in determining neuronal responses when challenged with kainic acid. In addition, the ability of the human immunodeficiency virus, transactivating protein to modulate NMDA signaling possibly triggering seizures, highlights the fact that elements of the antiviral response and even virally derived proteins are capable of directly manipulating neuronal function. Understanding the complex relationships between the CNS, the immune system, and invading pathogens is a critical step in understanding the pathogenesis of seizures seen during viral infections and informing the development of novel therapies.
%Z FOR Codes: 110804 110903 110704


%0 Journal Article
%~ PubMed
%A Müller, Marcus
%A Carter, Sally L
%A Hofer, Markus J
%A Manders, Peter
%A Getts, Daniel R
%A Getts, Meghan T
%A Dreykluft, Angela
%A Lu, Bao
%A Gerard, Craig
%A King, Nicholas J C
%A Campbell, Iain L
%T CXCR3 Signaling Reduces the Severity of Experimental Autoimmune Encephalomyelitis by Controlling the Parenchymal Distribution of Effector and Regulatory T Cells in the Central Nervous System.
%B Journal of immunology (Baltimore, Md. : 1950)
%D 2007
%C United States
%I American Association of Immunologists
%V 179
%N 5
%P 2774-2786
%@ 0022-1767
%X The chemokine receptor CXCR3 promotes the trafficking of activated T and NK cells in response to three ligands, CXCL9, CXCL10, and CXCL11. Although these chemokines are produced in the CNS in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), their role in the pathogenesis of CNS autoimmunity is unresolved. We examined the function of CXCR3 signaling in EAE using mice that were deficient for CXCR3 (CXCR3(-/-)). The time to onset and peak disease severity were similar for CXCR3(-/-) and wild-type (WT) animals; however, CXCR3(-/-) mice had more severe chronic disease with increased demyelination and axonal damage. The inflammatory lesions in WT mice consisted of well-demarcated perivascular mononuclear cell infiltrates, mainly in the spinal cord and cerebellum. In CXCR3(-/-) mice, these lesions were more widespread throughout the CNS and were diffused and poorly organized, with T cells and highly activated microglia/macrophages scattered throughout the white matter. Although the number of CD4(+) and CD8(+) T cells infiltrating the CNS were similar in CXCR3(-/-) and WT mice, Foxp3(+) regulatory T cells were significantly reduced in number and dispersed in CXCR3(-/-) mice. The expression of various chemokine and cytokine genes in the CNS was similar in CXCR3(-/-) and WT mice. The genes for the CXCR3 ligands were expressed predominantly in and/or immediately surrounding the mononuclear cell infiltrates. We conclude that in EAE, CXCR3 signaling constrains T cells to the perivascular space in the CNS and augments regulatory T cell recruitment and effector T cell interaction, thus limiting autoimmune-mediated tissue damage.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Kunzelmann, Karl
%A Sun, Jane
%A Meanger, Jayesh
%A King, Nicholas J
%A Cook, David I
%T Inhibition of airway Na+ transport by respiratory syncytial virus.
%B Journal of virology
%D 2007
%C US
%I American Society for Microbiology
%V 81
%N 8
%P 3714-20
%@ 0022-538X
%X In previous studies, we have shown that two major respiratory pathogens, influenza virus and parainfluenza virus, produce acute alterations in ion transport upon contacting the apical membrane of the respiratory epithelium. In the present study, we examine the effects on ion transport by the mouse tracheal epithelium of a third major respiratory pathogen, respiratory syncytial virus (RSV). RSV infections are associated with fluid accumulation in the respiratory tract and cause illnesses that range in severity from rhinitis, sinusitis, otitis media, and bronchitis to bronchiolitis and pneumonia. We find that within minutes of RSV contacting the apical membrane; it inhibits amiloride-sensitive Na+ transport by the epithelium. This effect is mediated by protein kinase C and is reproduced by recombinant viral F (fusion) protein. Since this inhibition is not accompanied by any alteration in the epithelial responses to carbachol or to forskolin plus 3-isobutyl-1-methylxanthine (IBMX), it is not due to a nonspecific toxic action of the virus. The inhibition also appears to require Toll-like receptor 4 and the presence of asialogangliosides in the apical membrane. Since the concentration range over which this inhibition is observed (10(2) to 10(5) PFU/ml) is comparable to the viral concentrations observed in clinical and experimental RSV infections, it seems likely that direct inhibition by the virus of epithelial Na+ transport may contribute to the fluid accumulation that is observed in RSV infections.
%Z FOR Codes: 110804


%0 Journal Article
%~ PubMed
%A King, Nicholas J C
%A Thomas, Shane R
%T Molecules in focus: Indoleamine 2,3-dioxygenase.
%B The international journal of biochemistry & cell biology
%D 2007
%C United Kingdom
%I Pergamon
%V 39
%N 12
%P 2167-72
%@ 1357-2725
%X Indoleamine 2,3-dioxygenase (IDO) is a heme enzyme that initiates the oxidative degradation of the least abundant, essential amino acid, l-tryptophan, along the kynurenine pathway. The local cellular depletion of l-tryptophan that results may enable the host to inhibit the growth of various infectious pathogens in vivo. However, over the past decade, it has become increasingly apparent that IDO also represents an important immune control enzyme. Thus, cells expressing IDO, seemingly paradoxically, are capable of suppressing local T cell responses to promote immune tolerance under various physiological and pathophysiological conditions of medical importance, including infectious diseases, foetal rejection, organ transplantation, neuropathology, inflammatory and auto-immune disorders and cancer. In this review, we briefly outline the biochemical properties of IDO, its known and hypothetical functions and the medical implications for inhibition or induction of IDO and/or its downstream catabolites in health and disease.
%Z FOR Codes: 110704


%0 Journal Article
%~ PubMed
%A Getts, Daniel R
%A Matsumoto, Izuru
%A Müller, Marcus
%A Getts, Meghann Teague
%A Radford, Jane
%A Shrestha, Bimmi
%A Campbell, Iain L
%A King, Nicholas J C
%T Role of IFN-gamma in an experimental murine model of West Nile virus-induced seizures.
%B Journal of neurochemistry
%D 2007
%C UK
%I Blackwell Publishing Ltd
%V 103
%N 3
%P 1019-30
%@ 1471-4159
%X Seizures are a major complication of viral encephalitis. However, the mechanisms of seizure-associated neuronal dysfunction remain poorly understood. We report that intranasal inoculation with West Nile virus (WNV) (Sarafend) causes limbic seizures in C57BL/6 mice, but not in interferon (IFN)-gamma-deficient (IFN-gamma-/-) mice. Both strains showed similar levels of virus in the brain, as well as similar concentrations of the cytokines, tumor necrosis factor and interleukin-6, both of which can alter neuronal excitability. Experiments in chimeric IFN-gamma-/- mice reconstituted with IFN-gamma-producing leukocytes showed that IFN-gamma is not required during central nervous system infection for limbic seizure development, suggesting a role for IFN-gamma in the developing brain. This was supported responses to pentylenetetrazole, kainic acid (KA), and N-methyl-d-aspartate (NMDA). Both strains of mice exhibited similar behavior after pentylenetetrazole challenge. However, while NMDA and KA treatment resulted in characteristic seizures in C57BL/6 mice, these responses were diminished (NMDA treatment) or absent (KA treatment) in IFN-gamma-/- mice. Furthermore, NMDA-receptor blockade with MK-801 in WNV-infected C57BL/6 mice abrogated seizures and prolonged survival. Our data show that IFN-gamma plays an important role in the development of the excitatory seizure pathways in the brain and that these cascades become pathogenic in encephalitic WNV infection.
%Z FOR Codes: 110704 110903 110804


%0 Journal Article
%~ PubMed
%A Wacher, Christie
%A Müller, Marcus
%A Hofer, Markus J
%A Getts, Daniel R
%A Zabaras, Regina
%A Ousman, Shalina S
%A Terenzi, Fulvia
%A Sen, Ganes C
%A King, Nicholas J C
%A Campbell, Iain L
%T Co-ordinate regulation and widespread cellular expression of the interferon stimulated genes (ISG)-49, ISG-54 and ISG-56 in the central nervous system following infection with distinct viruses.
%B Journal of Virology
%D 2006
%C US
%I American Society for Microbiology
%V 81
%N 2
%P 860-871
%@ 0022-538X
%X The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. We examined the simultaneous regulation of these ISGs in the brains of mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile virus (WNV). Expression of the ISG-49 and ISG-56 genes increased significantly during LCMV infection, being widespread and localized predominantly to common as well as distinct neuronal populations. Expression of the ISG-54 gene also increased but to lower levels and with a more restricted distribution. Although expression of the ISG-49, ISG-54, and ISG-56 genes was increased in the brains of LCMV-infected STAT1 and STAT2 knockout (KO) mice, this was blunted, delayed, and restricted to the choroid plexus, meninges, and endothelium. ISG-56 protein was regulated in parallel with the corresponding RNA transcript in the brain during LCMV infection in wild-type and STAT KO mice. Similar changes in ISG-49, ISG-54, and ISG-56 RNA levels and ISG-56 protein levels were observed in the brains of wild-type mice following infection with WNV. Thus, the ISG-49, ISG-54, and ISG-56 genes are coordinately upregulated in the brain during LCMV and WNV infection; this upregulation, in the case of LCMV, was totally (neurons) or partially (non-neurons) dependent on the IFN-signaling molecules STAT1 and STAT2. These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Jayasekera, Jerome P
%A Vinuesa, Carola G
%A Karupiah, Gunasegaran
%A King, Nicholas J C
%T Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice.
%B The Journal of general virology
%D 2006
%C UK
%I Society for General Microbiology
%V 87
%N Pt 11
%P 3361-71
%@ 0022-1317
%X NOS2 gene-deficient (NOS2(-/-)) mice are less susceptible than wild-type (NOS2(+/+)) mice to infection with Influenza A virus. Virus titres in the lungs of influenza-infected NOS2(-/-) mice are significantly lower than those in NOS2(+/+) mice, with enhanced viral clearance in NOS2(-/-) mice dependent on gamma interferon (IFN-gamma). The current study was undertaken to ascertain the role of specific components of the immune response in promoting virus clearance in influenza-infected NOS2(-/-) mice. Levels of T cell- and natural killer cell-mediated cytotoxicity in the lungs of virus-infected mice were not significantly different between NOS2(+/+) and NOS2(-/-) mice. However, virus-infected NOS2(-/-) mice produced higher levels of virus-specific IgG2a antibody. Furthermore, more viable B cells and plasmablasts, along with greater levels of IFN-gamma, were found in NOS2(-/-) splenocyte cultures stimulated with B-cell mitogens. In addition to the early reduction in virus titres, clinical symptoms and proinflammatory cytokine production were attenuated in NOS2(-/-) mice. Thus, NOS2(-/-) B cells are capable of responding rapidly to influenza virus infection by proliferating and preferentially producing antibody of the IgG2a subtype. The relationship between viral load and the development of immunopathology is discussed.
%Z FOR Codes: 110704 110804


%0 Journal Article
%~ PubMed
%A King, Nicholas J C
%A Getts, Daniel R
%A Getts, Meghann T
%A Rana, Sabita
%A Shrestha, Bimmi
%A Kesson, Alison M
%T Immunopathology of flavivirus infections.
%B Immunology and cell biology
%D 2006
%C UK
%I Nature Publishing Group
%V 85
%N 1
%P 33-42
%@ 0818-9641
%X With the recent emergence of the flavivirus, West Nile virus (WNV), in particular, the New York strain of Lineage I WNV in North America in 1999, there has been a significant increase in activity in neurotropic flavivirus research. These viruses cause encephalitis that can result in permanent neurological sequelae or death. Attempts to develop vaccines have made progress, but have been variably successful, despite considerable commercial underwriting. Thus, the discovery of ways and means to combat disease is no less urgent. As such, most recent work has been directed towards dissecting and understanding the pathogenesis of disease, as a way of informing possible approaches to abrogation or amelioration of illness. Whether inherent to flaviviruses or because humans are incidental, dead-end hosts, it is clear that these viruses interact with their human hosts in extremely complex ways. This occurs from the cellular level, at which infection must be established to produce disease, to its interaction with the adaptive immune response, which may result in its eradication, with or without immunopathological and consequent neurological sequelae. As human proximity to and contact with flavivirus insect vectors and amplifying hosts cannot practically be eliminated, our understanding of the pathogenesis of flavivirus-induced diseases, especially with regard to possible targets for treatment, is imperative.
%Z FOR Codes: 110704 110804 110903


%0 Journal Article
%~ PubMed
%A Oliver, Brian G G
%A Johnston, Sebastian L
%A Baraket, Melissa
%A Burgess, Janette K
%A King, Nicholas J C
%A Roth, Michael
%A Lim, Sam
%A Black, Judith L
%T Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection.
%B Respiratory research
%D 2006
%C United Kingdom
%I BioMed Central Ltd.
%V 7
%N 
%P 71
%@ 1465-993X
%X BACKGROUND: Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV) are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM). We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. METHODS: HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. RESULTS: RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-kappaB + AP-1 in the non-asthmatic HASM cells. CONCLUSION: This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.
%Z FOR Codes: 110701 110804