Activation of JNK and p38 pathways in Mesangial Cells (MC) stimulated by PDGF, but not IL-1, are inhibited by cAMP

PDGF stimulates mitogenesis and activates the ERK pathway in cultured MC. Increase in cAMP counteracts this activation. According to recent reports, other members of the MAPK family, JNK and p38, are present in MC. In view of this, we investigated on rat cultured MC whether a) PDGF activates also JNK and p38 pathways and, if so, b) whether activation is blocked by cAMP. Incubation of MC with PDGF increased significantly activity of JNK (2.5 times) and p38 (2 times) and even to a higher degree that activation of ERK. Addition of forskolin (FSK), a potent stimulator of adenylate cyclase, inhibited all three PDGF-activated kinases but to a significantly different degree: ERK (-44 + 6%); p38 (-69 + 9%); and JNK (-94 + 4%). While FSK inhibited "stress" pathways stimulated by PDGF to a greater degree than ERK, addition of FSK failed to inhibit p38 and JNK when stimulated by the pro-inflammatory cytokine IL-1. Results show that the single potent growth hormone, PDGF, can activate simultaneously all three members of the MAPK family in MC; however, the "negative crosstalk" with cAMP is of different extent.