Effect of mycophenolic acid on TNF alpha-induced expression of cell adhesion molecules in human venous endothelial cells in vitro

British Journal of Pharmacology
I A HauserM Goppelt-Strübe

Abstract

1. Mycophenolic acid (MPA) is an inhibitor of inosine-5'-monophosphate dehydrogenase and therefore interferes with cellular GTP biosynthesis. Recently, MPA has been used as an antiproliferative and immunosuppressive agent. In the present study, the effect of MPA on the expression of the endothelial cell adhesion molecules (CAMs), intercellular (I) CAM-1, vascular (V) CAM-1 and endothelial (E)-selectin, was investigated in tumour necrosis factor-alpha (TNF alpha)-activated cultured human venous endothelial cells (EC). 2. Surface expression of CAMs was measured by flow cytometry and mRNA expression by Northern blot analysis. Transcriptional activation of CAMs by the nuclear factor NF-kappaB was determined by an electromobility shift assay. The function of CAMs was studied by a static adhesion assay with human monocyte-like undifferentiated U937 cells. 3. Pretreatment of TNF alpha- (5 ng ml(-1), 12 h) activated EC with MPA (10 microM, 24 h) increased the binding of U937 cells, which had not been treated with MPA, by approximately 2 fold. MPA-pretreatment of EC did not affect TNF alpha-induced surface expression of ICAM-1. However, VCAM-1 and E-selectin were increased 2-3 fold and remained elevated up to 24 h, by which time TNF alp...Continue Reading

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Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.