PMID- 24829345
OWN - NLM
STAT- MEDLINE
DCOM- 20141001
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 88
IP  - 15
DP  - 2014 Aug
TI  - Interleukin-6 (IL-6) and IL-17 synergistically promote viral persistence by 
      inhibiting cellular apoptosis and cytotoxic T cell function.
PG  - 8479-89
LID - 10.1128/JVI.00724-14 [doi]
AB  - Interleukin-6 (IL-6) plays an important role in the development and progression 
      of inflammatory responses, autoimmune diseases, and cancers. Many viral 
      infections, including Theiler's murine encephalomyelitis virus (TMEV), result in 
      the vigorous production of IL-6. However, the role of IL-6 in the development of 
      virus-induced inflammatory responses is unclear. The infection of susceptible 
      mice with TMEV induces the development of chronic demyelinating disease, which is 
      considered a relevant infectious model for multiple sclerosis. In this study, we 
      demonstrate that resistant C57BL/6 mice carrying an IL-6 transgene (IL-6 Tg) 
      develop a TMEV-induced demyelinating disease accompanied by an increase in viral 
      persistence and an elevated Th17 cell response in the central nervous system. 
      Either IL-6 or IL-17 induced the expression of Bcl-2 and Bcl-xL at a high 
      concentration. The upregulated expression of prosurvival molecules in turn 
      inhibited target cell destruction by virus-specific CD8(+) T cells. More 
      interestingly, IL-6 and IL-17 synergistically promoted the expression of these 
      prosurvival molecules, preventing cellular apoptosis at a much lower (<5-fold) 
      concentration. The signals involved in the synergy appear to include the 
      activation of both STAT3 and NF-kappaB via distinct cytokine-dependent pathways. 
      Thus, the excessive IL-6 promotes the generation of Th17 cells, and the resulting 
      IL-6 and IL-17 synergistically promote viral persistence by protecting 
      virus-infected cells from apoptosis and CD8(+) T cell-mediated target 
      destruction. These results suggest that blocking both IL-6 and IL-17 functions 
      are important considerations for therapies of chronic viral diseases, autoimmune 
      diseases, and cancers. IMPORTANCE: This study indicates that an excessive level 
      of IL-6 cytokine produced following viral infection promotes the development of 
      IL-17-producing pathogenic helper T cells. We demonstrate here for the first time 
      that IL-6 together with IL-17 synergistically enhances the expression of survival 
      molecules to hinder critical host defense mechanisms removing virus-infected 
      cells. This finding has an important implication in controlling not only chronic 
      viral infections but also autoimmune diseases and cancers, which are associated 
      with prolonged cell survival.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Hou, Wanqiu
AU  - Hou W
AD  - Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern 
      University, Chicago, Illinois, USA.
FAU - Jin, Young-Hee
AU  - Jin YH
AD  - Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern 
      University, Chicago, Illinois, USA.
FAU - Kang, Hyun Seok
AU  - Kang HS
AD  - Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern 
      University, Chicago, Illinois, USA.
FAU - Kim, Byung S
AU  - Kim BS
AD  - Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern 
      University, Chicago, Illinois, USA bskim@northwestern.edu.
LA  - eng
GR  - R01 NS028752/NS/NINDS NIH HHS/United States
GR  - R01 NS033008/NS/NINDS NIH HHS/United States
GR  - R01 NS33008/NS/NINDS NIH HHS/United States
GR  - R01 NS28752/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140514
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-6)
RN  - 0 (interleukin-6, mouse)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Female
MH  - *Immune Evasion
MH  - Interleukin-17/*metabolism
MH  - Interleukin-6/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Theilovirus/*immunology/*physiology
PMC - PMC4135960
EDAT- 2014/05/16 06:00
MHDA- 2014/10/02 06:00
PMCR- 2015/02/01
CRDT- 2014/05/16 06:00
PHST- 2014/05/16 06:00 [entrez]
PHST- 2014/05/16 06:00 [pubmed]
PHST- 2014/10/02 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - JVI.00724-14 [pii]
AID - 00724-14 [pii]
AID - 10.1128/JVI.00724-14 [doi]
PST - ppublish
SO  - J Virol. 2014 Aug;88(15):8479-89. doi: 10.1128/JVI.00724-14. Epub 2014 May 14.