Butyrate and trichostatin A attenuate nuclear factor kappaB activation and tumor necrosis factor alpha secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells.
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Usami M, Kishimoto K, Ohata A, Miyoshi M, Aoyama M, Fueda Y, Kotani J
Butyrate and trichostatin A attenuate nuclear factor kappaB activation and tumor necrosis factor alpha secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells.
Nutr Res. 2008 May;28(5):321-8. doi: 10.1016/j.nutres.2008.02.012.
- PubMed ID
- 19083427 [ View in PubMed]
- 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)-alpha secretion and nuclear factor kappaB (NF-kappaB) activation in peripheral blood mononuclear cells induced with lipopolysaccharide were evaluated in relation to prostaglandin E(2) (PGE(2)) secretion. Treatment of cells with butyrate; tributyrin, a prodrug of butyrate; propionate; acetate; and TSA down-regulated TNF-alpha secretion but all up-regulated PGE(2) secretion. Butyrate, propionate, and TSA inhibited NF-kappaB 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-alpha secretion, and nordihydroguaiaretic acid inhibited that of acetate. The results showed that butyrate, propionate, and TSA inhibited TNF-alpha production via PGE(2) secretion and down-regulated NF-kappaB 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Indomethacin Human Cyclooxygenases (Protein Group) Protein group Humans YesInhibitorDetails Trichostatin A Prostaglandin E2 Receptors (Protein Group) Protein group Humans UnknownRegulatorDetails Trichostatin A Tumor necrosis factor Protein Humans UnknownDownregulatorDetails