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Double‐stranded RNA mediates interferon regulatory factor 3 activation and interleukin‐6 production by engaging Toll‐like receptor 3 in human brain astrocytes
Author(s) -
Kim Hyemi,
Yang Eunjung,
Lee Jeonggi,
Kim SeHoon,
Shin JeonSoo,
Park Joo Young,
Choi Sun Ju,
Kim Se Jong,
Choi InHong
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02799.x
Subject(s) - tlr3 , irf3 , interferon regulatory factors , biology , microbiology and biotechnology , toll like receptor , proinflammatory cytokine , interferon , signal transduction , p38 mitogen activated protein kinases , protein kinase r , tlr4 , kinase , protein kinase a , innate immune system , inflammation , immune system , immunology , mitogen activated protein kinase kinase
Summary Toll‐like receptor 3 (TLR3) participates in the innate immune response by recognizing viral pathogens. In this study, human brain astrocytes were found to constitutively express TLR3, and this expression was increased by interferon‐γ (IFN‐γ) or double‐stranded RNA (dsRNA). Treatment employing dsRNA in astrocytes induced IFN regulatory factor 3 (IRF3) phosphorylation, dimer formation and nuclear translocation followed by STAT1 activation. This treatment also activated nuclear factor‐κB, p38 and c‐Jun N‐terminal kinase significantly, while activating extracellular signal‐regulated kinase to a lesser extent. Treatment with anti‐TLR3 antibody inhibited dsRNA‐mediated interleukin‐6 (IL‐6) production. In the presence of mitogen‐activated protein kinase inhibitors, astrocytes failed to secrete IL‐6 in response to dsRNA treatment. Therefore, dsRNA‐induced IL‐6 production is dependent on mitogen‐activated protein kinases and type I IFN production is dependent on IRF3 in brain astrocytes. These results suggest that brain inflammation, which produces inflammatory cytokines and type I IFNs, may enhance TLR3 expression in astrocytes. Additionally, upregulated TLR3 might modulate inflammatory processes by producing proinflammatory cytokines.