Role of Src in poly(I:C)-induced interferon-beta (IFN-β)production in macrophages

• Main Authors: Yung-Kuo Li, 李永國
• Other Authors: 馬明琪
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/83296252262503115875

碩士 === 中國醫藥大學 === 基礎醫學研究所 === 98 === By recognizing double stranded RNA (dsRNA), a product of viral infection, TLR3 can produce type I interferons such interferon alpha and beta (i.e. IFNα/β) that possess anti-viral and immune modulating functions. As the synthetic analogue of dsRNA, polyinosinic-polycytidylic acid (poly(I:C)) can effectively induce the production of IFNα/β in macrophages. In this study, we investigated the signal transduction pathways in IFN-β secretion elicited by poly(I:C). We observed that poly(I:C)-mediated IFN-β generation was PP2 (an inhibitor for Src family kinases(SFKs)) sensitive in murine RAW264.7 cells. Pharmacological blockade of AG (an iNOS inhibitor) and ODQ (a sGC inhibitor) suppressed poly(I:C)-evoked IFN-β mRNA expression. Either SNAP (a NO donor) or 8-br-cGMP (a cGMP analogue) could rescue these defects. We found that the increment of IFN-β could be attributable to their increased transcripts. Interestingly, knockout of iNOS suppressed poly(I:C)-evoked IFN-β secretion and Src induction. Notably, attenuation of Src by src-specific siRNA reduced poly(I:C)-, and SNAP-enhanced IFN-β production in macrophages, and reintroduction of avain Src could rescue this defect. With these results, we concluded that iNOS was critical for poly(I:C)-mediated IFN-β production and Src played a pivotal role in this process.