title: Short-chain fatty acids and trichostatin A alter tight junction permeability in human umbilical vein endothelial cells.
abstract: OBJECTIVE
  The short-chain fatty acids (SCFAs), butyrate, propionate, and acetate, produced by bacterial fermentation of dietary fiber, can modulate the transcription of certain genes by inhibiting histone deacetylase in colonocytes and several other cell types in vitro. We previously reported that butyrate decreases tight junction permeability by activating lipoxygenase (LOX) in intestinal monolayer cells. In the present study, we evaluated the effects of SCFAs on tight junction permeability in an endothelial cell culture and their possible mechanisms of action via histone deacetylase inhibitor activity. We also investigated the factors modulating tight junction permeability.
  
  
  METHODS
  The effects of butyrate, propionate, and acetate on tight junction permeability in human umbilical vein endothelial cells were examined using Transwell chamber cultures. The contributions of inducible nitric oxide synthase (NOS), endothelial NOS, estrogen receptor, cyclo-oxygenase, and LOX to SCFAs' effects were also evaluated. The effects of SCFAs were compared with those of trichostatin A, a typical histone deacetylase inhibitor.
  
  
  RESULTS
  Low concentrations of butyrate and propionate decreased paracellular permeability without inducing cell damage. However, acetate decreased paracellular permeability in a concentration-dependent manner. An estrogen receptor antagonist attenuated the effects of SCFAs on tight junction permeability. The influences of inducible NOS, cyclo-oxygenase, and LOX inhibitors and the expressions of cyclo-oxygenase and LOX mRNAs were different for each SCFA. Trichostatin A slightly decreased paracellular permeability when used at lower concentrations, but higher concentrations of trichostatin A increased permeability.
  
  
  CONCLUSIONS
  The SCFAs play an important role in the assembly of tight junctions in normal vascular endothelial cells.
authors: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors: Makoto
authors: M
authors: Miyoshi
authors: Makoto
authors: M
authors: Usami
authors: Atsushi
authors: A
authors: Ohata
mesh_terms: D000085:Acetates / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects*; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D000085:Acetates; D002087:Butyrates; D005232:Fatty Acids, Volatile; D006877:Hydroxamic Acids; D011422:Propionates; C012589:trichostatin A; D008084:Lipoxygenase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases; D006655:Histone Deacetylases