Effects of mycophenolic Acid on the proliferation and endothelin-1 and interleukin-6 secretion of rat pulmonary microvascular endothelial cells.

OBJECTIVE To investigate the effect of mycophenolic acid (MPA) on the proliferation of rat pulmonary microvascular endothelial cells (PMVECs) and on the secretion of endothelin-1 (ET-1) and interleukin-6 (IL-6) by these cells. METHODS Rat PMVECs were treated with five different final concentrations of MPA (0, 0.1, 1, 10 and 100 μM). The fetal bovine serum-induced proliferation of the PMVECs was detected using the Cell Counting Kit-8 (CCK-8). The levels of ET-1 and IL-6 secretion were assessed by radioimmunoassays. RESULTS At the 24 h time point, the optical density (OD) values at 450 nm for the five groups showed that there were no significant differences between the groups treated with 0 and 0.1 μM MPA (P=0.388) or between the groups treated with 10 and 100 μM MPA (P=0.292), but the OD values were significantly different between all other pairs of groups (P<0.001). At the 48 h time point, the OD values at 450 nm for the five groups showed that there was no significant difference between the groups treated with 0 and 0.1 μM MPA (P=0.094), but the OD values were significantly different between all the other groups (P<0.001). At the 72 h time point, the OD values at 450 nm for the five groups showed that there was no significant difference between the groups treated with the final concentrations of 0 and 0.1 μM MPA (P=0.931), but the OD values were significantly different between all other pairs of groups (10 μM MPA vs 100 μM MPA: P=0.037; 0 μM MPA vs 1 μM MPA: P=0.006; 1 μM MPA vs 10 μM MPA: P=0.005; all other comparisons: P<0.001). There were no significant differences in ET-1 concentration between the groups treated with 0 and 0.1 μM MPA (P=0.156) or the groups treated with 10 and 100 μM MPA (P=0.262), but there were significant differences between all other pairs of groups (P<0.001). By contrast, there were no significant differences in IL-6 concentrations between any pair of groups (P>0.05). CONCLUSIONS MPA inhibits fetal bovine serum-induced rat PMVEC proliferation and ET-1 secretion in a dose-dependent manner.