Short-chain fatty acids modulate gene expression for vascular endothelial cell adhesion molecules

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Leukocyte infiltration into the intestinal wall is a key factor in inflammatory bowel disease pathogenesis.
• Endothelial adhesion molecules, such as ICAM-1 and E-selectin, mediate leukocyte migration.
• Short-chain fatty acids (SCFAs) from dietary fiber are known to reduce colon inflammation, but their effect on vascular adhesion molecules is unclear.

Purpose of the Study:

• To investigate the effects of SCFAs on vascular endothelial cell adhesion molecule expression.
• To determine if butyrate influences intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression in endothelial cells.

Main Methods:

• Human umbilical vein endothelial cells were treated with physiologically relevant concentrations of butyrate.
• Expression of ICAM-1 protein and mRNA, E-selectin, HLA-DR, vascular cell adhesion molecule-1, and endoglin were assessed.
• Effects of other SCFAs (valerate, isobutyrate, propionate) and a histone deacetylase inhibitor (trichostatin A) were also evaluated.

Main Results:

• Butyrate significantly increased endothelial expression of ICAM-1 protein and mRNA in a time-dependent manner.
• Butyrate also increased E-selectin expression but did not affect HLA-DR, vascular cell adhesion molecule-1, or endoglin.
• Valerate and propionate increased ICAM-1 expression, though less potently than butyrate, while isobutyrate had minimal effect.

Conclusions:

• Butyrate enhances the expression of ICAM-1 and E-selectin on vascular endothelial cells.
• These butyrate-induced changes in vascular adhesion molecules may play a role in modulating gut inflammation.
• Further in vivo studies are required to elucidate the role of SCFAs and dietary fiber in inflammatory bowel disease.