Double-stranded RNA mediates interferon regulatory factor 3 activation and interleukin-6 production by engaging Toll-like receptor 3 in human brain astrocytes
| Autor: | Eunjung Yang, Se Hoon Kim, Sun Ju Choi, In Hong Choi, Jeonggi Lee, Jeon Soo Shin, Joo Young Park, Hyemi Kim, Se Jong Kim |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
viruses
Polynucleotides Immunology Dose-Response Relationship Immunologic Electrophoretic Mobility Shift Assay Biology Mitogen-activated protein kinase kinase Proinflammatory cytokine Interferon-gamma Fetus NF-KappaB Inhibitor alpha Humans Immunology and Allergy Protein kinase A Cells Cultured RNA Double-Stranded Mitogen-Activated Protein Kinase Kinases Toll-like receptor Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction NF-kappa B Brain Original Articles Molecular biology Protein kinase R Toll-Like Receptor 3 Up-Regulation STAT1 Transcription Factor Astrocytes Mitogen-activated protein kinase TLR3 biology.protein I-kappa B Proteins Interferon Regulatory Factor-3 IRF3 |
| Zdroj: | Immunology. 124:480-488 |
| ISSN: | 1365-2567 0019-2805 |
| Popis: | 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-gamma (IFN-gamma) 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-kappaB, 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. |
| Databáze: | OpenAIRE |
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