Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM‐1

Background Leukocyte recruitment to areas of inflammation depends on Integrin‐VCAM/ICAM interaction. Blocking the vascular cell adhesion molecule (VCAM‐1) and the intracellular adhesion molecule (ICAM‐1) may have therapeutic benefit for the inflammatory component of bowel disease. Notably, the induction of ICAM and VCAM is mediated by a nuclear factor kappaB (NF‐κB)‐dependent mechanism. We investigated whether the anti‐inflammatory properties of butyrate are mediated via the modulation of VCAM and ICAM on human endothelial cells. Methods VCAM‐1 and ICAM‐1 expression on human endothelial cells upon tumor necrosis factor‐α (TNF‐α) stimulation was assessd by FACS analysis. A monocyte adhesion assay was performed to evaluate the relevance of a modulated CAM‐expression. Electrophoretic mobility shift assays were applied to investigate NF‐κB activation. Results The observed butyrate‐associated inhibition of monocyte adhesion to endothelial cells is associated with an inhibition of NF‐κB activation in human endothelial cells. In this context, the observed suppression of the TNF‐α induced VCAM‐1 expression is likely to play an essential role. Conclusions Butyrate inhibits VCAM‐1 mediated leukocyte adhesion to human endothelial cells. This inhibition may contribute to the anti‐inflammatory effects of butyrate in patients with distal ulcerative colitis.