Role of mitogen-activated protein kinases in pulmonary endothelial cells exposed to cyclic strain

The aim of this study was to examine the role of mitogen-activated protein kinases (MAPKs) activation in bovine pulmonary arterial endothelial cells ( EC) exposed to cyclic strain. EC were subjected to 10% average strain at 60 cycles/min. Cyclic strain induced activation of extracellular signal-regul ated kinase (ERK; 1.5-fold), c-Jun NH2-terminal protein kinase (JNK; 1.9-fo ld), and p38 (1.5-fold) with a peak at 30 min. To investigate the functiona l role of the activated MAPKs, we analyzed cells after treatment with PD-98 059, a specific ERK kinase inhibitor, or SB-203580, a catalytic inhibitor f or p38, and after transient transfection with JNK(KR), and MEKK(K-M) the re spective catalytically inactive mutants of JNK1 and MAPK kinase kinase-l. C yclic strain increased activator protein-1 (AP-1) binding activity, which w as blocked by PD-98059 and SB-203580. Activity of AP-1-dependent luciferase reporter driven by 12-O-tetradecanoylphorbol-13-acetate-responsive element (TRE) was induced by cyclic strain, and this was attenuated by PD-98059, M EKK(K-M), JNK(K-R), and SB-203580. PD-98059 and SB-203850 did not inhibit c ell alignment and migration induced by cyclic strain. MEKK(K-M) and JNK(K-R ) transfection did not block cyclic strain-induced cell alignment. In concl usion, cyclic strain activates ERK, JNK, and p38, and their activation play s a role in transcriptional activation of AP-1/TRE but not in cell alignmen t and migration changes in bovine pulmonary arterial EC.