Short-chain fatty acids alter tight junction permeability in intestinal monolayer cells via lipoxygenase activation

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 21; no. 7; pp. 838 - 847
• Main Authors: Ohata, Atsushi, Usami, Makoto, Miyoshi, Makoto
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2005; Elsevier; Elsevier Limited
• Subjects: acetates; Acetylation; Apoptosis; Biological and medical sciences; Butyrate; butyrates; Butyrates - metabolism; Butyrates - pharmacology; Caco-2 Cells; cell culture; cell differentiation; cellular damage; Cyclooxygenase Inhibitors - pharmacology; Enzyme Activation; Fatty acids; Fatty Acids, Volatile - metabolism; Fatty Acids, Volatile - pharmacology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Histone acetylation; histones; Histones - metabolism; Humans; Hydroxyeicosatetraenoic acid; Inhibitors; Insulin; Insulin-like growth factors; intestinal absorption; intestinal mucosa; Kinases; Lipoxygenase; Lipoxygenase - genetics; Lipoxygenase - metabolism; Lipoxygenase Inhibitors - pharmacology; messenger RNA; Nitric oxide; nutrition-genotype interaction; Permeability; propionates; prostaglandin synthase; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Short-chain fatty acids; Tight junction permeability; tight junctions; Tight Junctions - drug effects; Tight Junctions - metabolism; Trichostatin A; Tumor Cells, Cultured; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Short-chain fatty acids; Tight junction permeability; Hydroxyeicosatetraenoic acid; Histone acetylation; Trichostatin A; Lipoxygenase; Butyrate; Short chain; Digestive system; Enzyme; Gut; Cell junction; Lipids; Activation; Permeability; Fatty acids; Vertebrata; Mammalia; Tight junction; Oxidoreductases; Acetylation; Histone
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2004.12.004

Involvement of lipoxygenase (LOX) and cyclo-oxygenase (COX) on cellular differentiation or apoptosis induced by butyrate has been reported recently, but the effect on tight junction (TJ) permeability has not been reported. One major activity of butyrate and, to a lesser extent, propionate is to modulate gene transcription via histone acetylation by their histone deacetylase inhibitor activity. In this study, we evaluated the activation of LOX and COX in TJ permeability changes by short-chain fatty acids, butyrate, propionate, and acetate in intestinal monolayer cells and their possible mechanism by histone acetylation. The effects of LOX and COX inhibitors on TJ permeability and the expression of LOX or COX mRNA induced by short-chain fatty acids were investigated in Caco-2 cells using Transwell chambers. The effects of hydroxyeicosatetraenoic acid (a product of LOX) on TJ permeability were also evaluated. The effects of short-chain fatty acids were compared with those of trichostatin A (histone deacetylase inhibitor). A LOX inhibitor clearly inhibited the effect of butyrate on TJ permeability, whereas COX inhibitors did not. The LOX and COX inhibitors partly inhibited the effects of propionate but not of acetate. Butyrate increased LOX mRNA expression, and hydroxyeicosatetraenoic acid and trichostatin A mimicked its effect. These results suggest that short-chain fatty acids, especially butyrate, induce TJ permeability changes through LOX activation through histone acetylation.