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.
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.
Authors: Zuojia Chen; Jialie Luo; Jian Li; Girak Kim; Eric S Chen; Sheng Xiao; Scott B Snapper; Bin Bao; Dingding An; Richard S Blumberg; Cheng-Hui Lin; Sui Wang; Jiaxin Zhong; Kuai Liu; Qiyuan Li; Chuan Wu; Vijay K Kuchroo Journal: J Exp Med Date: 2021-07-21 Impact factor: 14.307