title: Src is required for migration, phagocytosis, and interferon beta production in Toll-like receptor-engaged macrophages.
abstract: As an evolutionarily conserved mechanism, innate immunity controls self-nonself discrimination to protect a host from invasive pathogens. Macrophages are major participants of the innate immune system. Through the activation of diverse Toll-like receptors (TLRs), macrophages are triggered to initiate a variety of functions including locomotion, phagocytosis, and secretion of cytokines that requires the participation of tyrosine kinases. Fgr, Hck, and Lyn are myeloid-specific Src family kinases. Despite their constitutively high expression in macrophages, their absence does not impair LPS responsiveness. In contrast, Src, a barely detectable tyrosine kinase in resting macrophages, becomes greatly inducible in response to TLR engagement, implicating its role in macrophage activation. Indeed, silencing Src suppresses the activated TLR-mediated migration, phagocytosis, and interferon-beta (IFN-β) secretion in macrophages. And these physiological defects can be restored by the introduction of siRNA-resistant Src. Notably, the elevated expression and activity of Src is inducible nitric oxide synthase (iNOS)-dependent. Due to (1) iNOS being a NF-κB target, which can be induced by various TLR ligands, (2) Src can mediate NF-κB activation, therefore, there ought to exist a loop of signal amplification that regulates macrophage physiology in response to the engagement of TLRs.
authors: Graduate Institute of Basic Medical Science, China Medical University, 404, Taichung, Taiwan. mcmaa@mail.cmu.edu.tw.
authors: Ming-Chei
authors: MC
authors: Maa
authors: Institute of Basic Medical Sciences, China Medical University, 404, Taichung, Taiwan.|Department of Pharmacology, China Medical University, 404, Taichung, Taiwan.|Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, 701, Tainan, Taiwan.|Department of Pharmacology, College of Medicine, National Cheng Kung University, 701, Tainan, Taiwan.
authors: Tzeng-Horng
authors: TH
authors: Leu
keywords: IFN-β; Macrophage activation; Src; Toll-like receptors