Tight junction permeability is regulated by short-chain fatty acids like butyrate (in vitro estrogen)
Nutrition. 2008 Nov-Dec;24(11-12):1189-98. Epub 2008 Aug 23.
*
Short-chain fatty acids and trichostatin A alter tight junction
permeability in human umbilical vein endothelial cells.
Miyoshi M, Usami M, Ohata A.
Division of Nutrition and Metabolism, Kobe University Graduate School of
Health Sciences, Kobe, Japan.
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. CONCLUSION: The
SCFAs play an important role in the assembly of tight junctions in
normal vascular endothelial cells.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 18723323
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