The Journal of Nutritional Biochemistry
Volume 21, Issue 12 , Pages 1186-1192, December 2010

Butyrate reduced lipopolysaccharide-mediated macrophage migration by suppression of Src enhancement and focal adhesion kinase activity☆

  • Ming-Chei Maa

      Affiliations

    • Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan 40402, R.O.C.
    • Institute of Medical Science, China Medical University, Taichung, Taiwan 40402, R.O.C.
    • Corresponding Author InformationCorresponding authors. Ming-Chei Maa is to be contacted at Tel.: +886 4 2205 2121x7708; fax: +886 4 2205 3764. Tzeng-Horng Leu, Tel.: +886 6 235 3535x5468; fax: +886 6 274 9269.
    • ,
  • Miao Ying Chang

      Affiliations

    • Department of Medical Research, China Medical University Hospital, Taichung, Taiwan 40402, R.O.C.
    • ,
  • Ming-Yu Hsieh

      Affiliations

    • Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan 40402, R.O.C.
    • ,
  • Yen-Jen Chen

      Affiliations

    • Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, R.O.C.
    • Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, R.O.C.
    • ,
  • Ching-Jau Yang

      Affiliations

    • Institute of Medical Science, China Medical University, Taichung, Taiwan 40402, R.O.C.
    • ,
  • Zuei-Ching Chen

      Affiliations

    • Institute of Medical Science, China Medical University, Taichung, Taiwan 40402, R.O.C.
    • ,
  • Yung Kuo Li

      Affiliations

    • Institute of Medical Science, China Medical University, Taichung, Taiwan 40402, R.O.C.
    • ,
  • Chia-Kuang Yen

      Affiliations

    • Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan 40402, R.O.C.
    • ,
  • Ruei-Ren Wu

      Affiliations

    • Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan 40402, R.O.C.
    • ,
  • Tzeng-Horng Leu

      Affiliations

    • Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, R.O.C.
    • Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, R.O.C.
    • Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan, Taiwan 70101, R.O.C.
    • Corresponding Author InformationCorresponding authors. Ming-Chei Maa is to be contacted at Tel.: +886 4 2205 2121x7708; fax: +886 4 2205 3764. Tzeng-Horng Leu, Tel.: +886 6 235 3535x5468; fax: +886 6 274 9269.

Received 8 July 2009; received in revised form 14 October 2009; accepted 20 October 2009. published online 10 February 2010.

Abstract 

Macrophage motility is vital in innate immunity. Lipopolysaccharide (LPS)-mediated macrophage migration requires the enhancement of Src expression and enzymatic activity, which can be regulated by inducible nitric oxide synthase (iNOS). As a major short-chain fatty acid with histone deacetylase (HDAC) inhibitor activity, butyrate exerts anti-inflammatory effect by regulating the expression of cytokines. However, the influence of butyrate on macrophage movement was vague. In this study, we observed that butyrate inhibited migration of both RAW264.7 and rat peritoneal macrophages elicited by LPS. Unlike its myeloid relatives (i.e. Lyn, Fgr and Hck) whose expression was almost unaltered in the presence or absence of butyrate in LPS-treated macrophages, LPS-mediated Src induction was greatly suppressed by butyrate and that could be attributable to reduced level of the src transcript. Similar phenomenon was also detected in LPS-treated macrophages exposed to another HDAC inhibitor, trichostatin A (TSA). Consistent with the indispensability of iNOS in promoting macrophage mobilization via Src up-regulation and the activation of both Src and FAK, we did observe concomitant decrement of iNOS, Src and the suppressed activity of Src and FAK in butyrate- or TSA-pretreated macrophages following LPS exposure. These results imply that by virtue of reduction of Src, butyrate could effectively hamper LPS-triggered macrophage locomotion.

Keywords: Butyrate, Lipopolysaccharide, Src, FAK, macrophage migration

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☆ This work was supported by National Science Council grants to M.-C.M (NSC98-2311-B-039-002-MY3) and T.-H.L (NSC97-2320-B-006-024-MY3). Additional support came from NHRI (NHRI-EX-98-9828BI) and China Medical University (CMU97-103 and CMU97-193) to T.-H.L. and M.-C.M., respectively.

PII: S0955-2863(09)00218-6

doi:10.1016/j.jnutbio.2009.10.004

The Journal of Nutritional Biochemistry
Volume 21, Issue 12 , Pages 1186-1192, December 2010

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