Butyrate and trichostatin A attenuate nuclear factor κB activation and tumor necrosis factor α secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells |
| |
Authors: | Makoto Usami Kazunori Kishimoto Atsushi Ohata Makoto Miyoshi Michiko Aoyama Yuri Fueda Joji Kotani |
| |
Affiliation: | aDivision of Surgical Metabolism, Faculty of Health Science, Kobe University School of Medicine, Kobe, Japan;bDepartment of Medical Technology, Faculty of Health Science, Kagawa Prefectural College of Health Sciences, Japan;cDepartment of Emergency and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Japan |
| |
Abstract: | The effects of short-chain fatty acids (butyrate, propionate, and acetate) and trichostatin A (TSA), a typical histone deacetylase inhibitor, on tumor necrosis factor (TNF)-α secretion and nuclear factor κB (NF-κB) activation in peripheral blood mononuclear cells induced with lipopolysaccharide were evaluated in relation to prostaglandin E2 (PGE2) secretion. Treatment of cells with butyrate; tributyrin, a prodrug of butyrate; propionate; acetate; and TSA down-regulated TNF-α secretion but all up-regulated PGE2 secretion. Butyrate, propionate, and TSA inhibited NF-κB activation. The effects of the cyclooxygenase-nonspecific inhibitor, indomethacin; the cyclooxygenase-2 selective inhibitor, N-[2-(cyclohexyloxy)-4-nitro-phenyl] methanesulfonamide; and the general lipoxygenase inhibitor, nordihydroguaiaretic acid, varied in cells treated with each short-chain fatty acids. N-[2-(cyclohexyloxy)-4-nitro-phenyl] methanesulfonamide inhibited the effect of propionate on TNF-α secretion, and nordihydroguaiaretic acid inhibited that of acetate. The results showed that butyrate, propionate, and TSA inhibited TNF-α production via PGE2 secretion and down-regulated NF-κB activation by lipopolysaccharide. These data suggest that the mechanism of butyrate and propionate action is through histone deacetylation and acetate through lipoxygenase activation in the regulation of proinflammatory responses in cells. |
| |
Keywords: | Short-chain fatty acids Tumor necrosis factor α Nuclear factor κ B Prostaglandin E2 Histone deacetylase inhibitor Human peripheral blood mononuclear cells |
本文献已被 ScienceDirect 等数据库收录! |
|