Butyrate reduced lipopolysaccharide-mediated macrophage migration by suppression of Src enhancement and focal adhesion kinase activity.
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.
Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan 40402, R.O.C. mcmaa@mail.cmu.edu.tw
Ming-Chei
MC
Maa
Miao Ying
MY
Chang
Ming-Yu
MY
Hsieh
Yen-Jen
YJ
Chen
Ching-Jau
CJ
Yang
Zuei-Ching
ZC
Chen
Yung Kuo
YK
Li
Chia-Kuang
CK
Yen
Ruei-Ren
RR
Wu
Tzeng-Horng
TH
Leu
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002478:Cells, Cultured; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002087:Butyrates; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases