| Summary: | 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.
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