Mycophenolic acid influences T helper 2 (Th2) cytokine induced expression of intercellular cell adhesion molecule-1 (ICAM-1) on human endothelial cells

A possible synergistic effect of mycophenolic acid (NIPA) and the immunosup pressive cytokines IL-LY, IL-10 and IL-13 was investigated in human umbilic al vein endothelial cells (HUVEC). These cytokines, which are produced by T h2-lymphocytes, were shown to induce the expression of vascular cell adhesi on molecule-1 (VCAM-1) and production of IL-6 in endothelial cells. In this study we found IL-4 to induce both intercellular cell adhesion molecule-1 (ICAM-1) and VCAM-1 expression, whereas IL-13 induced VCAM-1 only. The surf ace expression of E-selectin was not influenced by any of the cytokines tes ted. MPA on its own led to statistically significant ICAM-1 expression on H UVEC. The combination of MPA with IL-4 led to a significant ICAM-1 expressi on in an additive manner compared to the cytokine alone. In contrast, MPA n either induced VCAM-1 nor did it influence the effects of IL-4 and IL-13 on VCAM-1 expression. A clinically relevant concentration of mycophenolic aci d (10 mu mol/l) decreased intracellular guanosine-5'-triphosphate (GTP) lev els significantly. Since intracellular nucleotides are responsible for the glycosylation of proteins, a disturbance of the endothelial nucleotide bala nce could be responsible for the effects of MPA on ICAM-1. Guanine and guan osine prevented and partially reversed the actions of MPA, on both intracel lular GTP and ICAM-1 expression, which strongly implies that MPA by interfe ring with nucleotide metabolism, affects the adhesive properties of endothe lial cells, and by acting synergistically with IL-4 probably influences Th2 cytokine effects.