COX-2 and cytosolic PLA2 mediate IL-1beta-induced cAMP production in human vascular smooth muscle cells (original) (raw)

Interleukin (IL)-1 is a potent vasodilator that causes prolonged induction of prostacyclin (PGI2) and cAMP synthesis in human vascular smooth muscle cells (HVSMC). The present study investigated IL-1 induction of PG synthetic enzymes in HVSMC and tested their respective roles in PGI2 and cAMP production. Cyclooxygenase (COX)-1 mRNA was not detectable in either control or IL-1-treated HVSMC, as assessed by RT-PCR. In contrast, COX-2 mRNA was detectable in control HVSMC, increased markedly (16-fold) after 1 h of IL-1 exposure, and increased further (52-fold) after 24 h. COX-2 protein levels, assessed by Western analysis, were increased concomitantly. HVSMC contained mRNA encoding both the secreted and cytosolic forms of phospholipase A2 (sPLA2 and cPLA2, respectively). IL-1 stimulation did not affect sPLA2 mRNA levels, but cPLA2 mRNA levels increased at 8 h, after the initial induction of PG synthesis. HVSMC constitutively expressed PGI2 synthase mRNA, and its levels were not affected...