Requirement of inducible nitric-oxide synthase in poly(I:C)-mediated Src induction and macrophage migration

• Main Authors: Ching-Jau Yang, 楊青昭
• Other Authors: 馬明琪
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/60999561531795036931

碩士 === 中國醫藥大學 === 基礎醫學研究所 === 97 === Toll-like receptors (TLRs) recognize different pathogen-associated molecular patterns (PAMPs), trigger the activation of innate immunity, and induce antimicrobial immune responses. TLR3 recognizes double- stranded RNA (dsRNA), a byproduct of viral infection, and polyinosinic- polycytidylic acid (poly(I:C)) is its synthetic analogue. In this study, we investigated the signal transduction pathways in cell mobility induced by poly(I:C) in macrophages. We observed that poly(I:C) elicited macrophage migration, and this event was PP2 (an inhibitor for Src family kinases (SFKs))-sensitive. Analysis of the expression of Src and its myeloid-specific relatives revealed that Src was upregulated by poly(I:C) while the amounts of Lyn, Fgr and Hck were kept almost constant. Similar phenomenon could also be detected in rat peritoneal macrophages exposed to poly(I:C). Intriguingly, attenuation of Src by src-specific siRNA reduced poly(I:C)-evoked mobilization, and suppressed FAK Pi-Tyr861 (FAK-pY861) in Raw264.7 macrophages and reintroduction of siRNA-resistant Src could rescue these events. Give that FAK played a pivotal role in macrophage mobility, our findings demonstrated that Src/FAK axis occupied a central role in poly(I:C)- elicited macrophage locomotion.　 Notably, compared to wild type macrophages, suppressed motility and Src induction were observed in iNOS-/- macrophages following poly(I:C) stimulation. With these findings, we concluded that iNOS was important in poly(I:C)-mediated Src upregulation and macrophage movement.