Role of Src in poly(I:C)-induced interleukin-1β (IL-1β) production in macrophage

• Main Authors: Po-yu Chuang, 莊博佑
• Other Authors: Ming-Chei Maa
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/23370103888397093777

碩士 === 中國醫藥大學 === 基礎醫學研究所碩士班 === 100 === TLR3 identified as recognizing of double-stranded RNA (dsRNA) and cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). IL-1β is a important cytokine in macrophages by trigger the synthetic analog of double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (polyI:C). In this study, we investigated the signal transduction pathways in IL-1β secretion promoted by polyI:C . We observed that polyI:C-mediated IL-1β production 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) decreased polyI:C-evoked IL-1β secretion. Either SNAP (a NO donor) or 8-br-cGMP (a cGMP analogue) could retrieve these defects. Interestingly, iNOS suppressed IL-1β secretion and Src induction by polyI:C in iNOS knockout mice. In particular, attenuation of Src by src-specific siRNA reduced polyI:C-IL-1β production in macrophages, and reintroduction of avain Src could rescue the defect. With these results, we concluded that iNOS was central for polyI:C-mediated IL-1β secretion and Src played a critical role in the course.