Berberine reduces Toll-like receptor-mediated macrophage migration by suppression of Src enhancement

Berberine is an isoquinoline with anti-inflammatory activity. We previously demonstrated that there was a loop of signal amplification between nuclear factor kappa B and Src for macrophage mobility triggered by the engagement of Toll like receptors (TLRs). The simultaneous suppression of lipopoly-saccharicle (LPS) mediated upregulation of inducible nitric oxide synthase, cyclooxygenase 2, and cell mobility in berberine-treated macrophages suggested Sic might be a target of berberine. Indeed, th reduced migration, greatly suppressed Sic induction in both protein and RNA transcript by berberine were observed in macrophages exposed to LPS, peptidoglycan, polyinosinic-polycytidylic acid, and CpG-oligodeoxynucleotides. In addition to Sic induction, berberine also inhibited LPS-mediated Sic activation in Sic overexpressing macrophages and S-nitroso-N-acetylpenicillamine (a nitric oxide donor) could partly restore it. Moreover, berberine suppressed Sic activity in fibronectin-stimulated macrophages and in v-Src transformed cells. These results implied that by effectively reducing Sic expression and activity, berberine inhibited TLR-mediated cell motility in macrophages. (C) 2015 Elsevier B.V. All rights reserved.