Berberine reduced lipopolysaccharide-mediated macrophage migration by suppression of Src enhancement

Autor: Jyun-Yan Wei, 魏均晏
Rok vydání: 2011
Druh dokumentu: 學位論文 ; thesis
Popis: 99
Toll-like receptors (TLRs) are important for macrophages to recognize foreign insults and induce the secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNFα). TLR4 can recognize lipopolysaccharide (LPS), and lipopolysaccharide (LPS)-mediated macrophage migration requires the enhancement of Src expression and enzymatic activity, which turned to be inducible nitric oxide synthase (iNOS)-dependent. Berberine is an alkaloid, which is present in Oregon grape. Previously, we have demonstrated that LPS could elicite macrophage migration by augmenting Src expression. Considered the implication of berberine in inflammation, we checked its effect on LPS-mediated macrophage mobility. In this study, we observed that berberine inhibited migration of RAW264.7 elicited by LPS. Unlike the other Src family kinases (SFKs) such as Lyn, Fgr, Hck whose expression was almost unaltered in the presence or absence of berberine in LPS-treated macrophages, the expression of Src was greatly induced by LPS and markedly reduced by berberine. Consistent with the indispensability of iNOS that can up-regulate Src and increase the activity of Src and FAK, we observed the decrement of LPS-elicited iNOS, Src and the level of FAK Pi-Tyr861 in macrophages pretreated with berberine. These results indicated that by decreasing the amount of iNOS and Src, berberine was capable to suppress macrophage locomotion upon LPS exposure.
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