Control of early Theiler's murine encephalomyelitis virus replication in macrophages by interleukin-6 occurs in conjunction with STAT1 activation and nitric oxide production
| Autor: | Tyler C. Moore, Thomas M. Petro, Liz A. Cody, Katherine L. Bush, Deborah Brown |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Lipopolysaccharides STAT3 Transcription Factor Lipopolysaccharide MAP Kinase Signaling System viruses Immunology Nitric Oxide Virus Replication Microbiology Nitric oxide Cell Line chemistry.chemical_compound Mice Theilovirus Virology Macrophage Animals STAT1 Interleukin 6 Extracellular Signal-Regulated MAP Kinases biology Kinase Interleukin-6 Macrophages virus diseases Molecular biology nervous system diseases STAT1 Transcription Factor chemistry Viral replication Insect Science biology.protein Pathogenesis and Immunity Female RNA Interference |
| Zdroj: | Journal of virology. 86(19) |
| ISSN: | 1098-5514 |
| Popis: | During Theiler's murine encephalomyelitis virus (TMEV) infection of macrophages, it is thought that high interleukin-6 (IL-6) levels contribute to the demyelinating disease found in chronically infected SJL/J mice but absent in B10.S mice capable of clearing the infection. Therefore, IL-6 expression was measured in TMEV-susceptible SJL/J and TMEV-resistant B10.S macrophages during their infection with TMEV DA strain or responses to lipopolysaccharide (LPS) or poly(I · C). Unexpectedly, IL-6 production was greater in B10.S macrophages than SJL/J macrophages during the first 24 h after stimulation with TMEV, LPS, or poly(I · C). Further experiments showed that in B10.S, SJL/J, and RAW264.7 macrophage cells, IL-6 expression was dependent on extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) and enhanced by exogenous IL-12. In SJL/J and RAW264.7 macrophages, exogenous IL-6 resulted in decreased TMEV replication, earlier activation of STAT1 and STAT3, production of nitric oxide, and earlier upregulation of several antiviral genes downstream of STAT1. However, neither inhibition of IL-6-induced nitric oxide nor knockdown of STAT1 diminished the early antiviral effect of exogenous IL-6. In addition, neutralization of endogenous IL-6 from SJL/J macrophages with Fab antibodies did not exacerbate early TMEV infection. Therefore, endogenous IL-6 expression after TMEV infection is dependent on ERK MAPK, enhanced by IL-12, but too slow to decrease viral replication during early infection. In contrast, exogenous IL-6 enhances macrophage control of TMEV infection through preemptive antiviral nitric oxide production and antiviral STAT1 activation. These results indicate that immediate-early production of IL-6 could protect macrophages from TMEV infection. |
| Databáze: | OpenAIRE |
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