| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Double-stranded RNA (dsRNA) and the viral RNA mimic, polyinosine-polycytidylic acid (poly(I : C)), are recognized by toll-like receptor 3 (TLR3) that mediates the innate immune response to viral infections. In this study, we investigated the effects of poly(I : C) on the production of chemokines (IL-8, RANTES, and eotaxin), Type I IFNs (IFNalpha and IFNbeta), Th1-cytokines (IL-12 and IF gamma), and pro-inflammatory cytokines (TNF-alpha and IL-1beta) by human nasal mucosa-derived fibroblasts. Human nasal fibroblasts were treated with poly(I : C), and levels of cytokines and chemokines were measured by ELISA. Incubation with poly(I : C) significantly enhanced the secretion of RANTES and IL-8. However, eotaxin, IL-1beta, TNF-alpha, IFNalpha, IF gamma, and IL-12 were not secreted from nasal fibroblasts stimulated with poly(I : C). The JNK inhibitor SP600125 and the PI3-kinase inhibitor LY294002 significantly blocked the poly(I : C)-induced release of RANTES and IL-8, whereas the p38 MAP kinase inhibitor SB203580 suppressed poly(I : C)-induced secretion of IL-8, but not RANTES. Nasal fibroblasts play an important role in initiating antiviral responses and inflammation of the nasal cavity by producing chemokines leading to enhanced inflammatory cell recruitment.
We also observed IL-4-induced Eotaxin production from nasal fibroblasts and the effect of. poly(I : C). PolyI : C reinforced the Eotaxin production with IL-4 significantly. IL-4-induced Eotaxin production was suppressed significantly with U0126. Furthermore IL-4-induced Eotaxin production from nasal fibroblasts was found that it is influenced in the revelation quantity of SOCS5.
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