title: Berberine reduces Toll-like receptor-mediated macrophage migration by suppression of Src enhancement.
abstract: 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 lipopolysaccharide (LPS)-mediated upregulation of inducible nitric oxide synthase, cyclooxygenase 2, and cell mobility in berberine-treated macrophages suggested Src might be a target of berberine. Indeed, th reduced migration, greatly suppressed Src 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 Src induction, berberine also inhibited LPS-mediated Src activation in Src overexpressing macrophages and S-nitroso-N-acetylpenicillamine (a nitric oxide donor) could partly restore it. Moreover, berberine suppressed Src activity in fibronectin-stimulated macrophages and in v-Src transformed cells. These results implied that by effectively reducing Src expression and activity, berberine inhibited TLR-mediated cell motility in macrophages.
authors: Graduate Institute of Clinical Science, China Medical University, Taichung, Taiwan, ROC; Division of Pulmonary and Critical Care Medicine, Department of Internal medicine, China Medical University Hospital, Taichung, Taiwan, ROC.
authors: Wei-Erh
authors: WE
authors: Cheng
authors: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC.
authors: Miao
authors: M
authors: Ying Chang
authors: Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan, ROC.
authors: Jyun-Yan
authors: JY
authors: Wei
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: Yen-Jen
authors: YJ
authors: Chen
authors: Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan, ROC; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC. Electronic address: mcmaa@mail.cmu.edu.tw.
authors: Ming-Chei
authors: MC
authors: Maa
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: tzengleu@mail.ncku.edu.tw.
authors: Tzeng-Horng
authors: TH
authors: Leu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology; D011066:Poly C / Q000494:pharmacology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D010457:Peptidoglycan; D051193:Toll-Like Receptors; D001599:Berberine; D011066:Poly C; D016392:Proto-Oncogene Proteins pp60(c-src)
keywords: Berberine; Berberine (PubChem CID: 2353); LPS (PubChem CID: 53481793); Macrophage migration; SNAP (PubChem CID: 5231); Src; Thioglycollate (PubChem CID: 5086465); Toll-like receptor