Interleukin 1 Induces Prostacyclin-Dependent Increases in Cyclic Amp Production and Does Not Affect Cyclic Gmp Production in Human Vascular Smooth Muscle Cells.

Author： Beasley D. McGuiggin M.E.

Publisher： Academic Press

ISSN： 1043-4666

Source： Cytokine, Vol.7, Iss.5, 1995-07, pp. : 417-426

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Abstract

Interleukin 1 (IL-1) is a pro-inflammatory cytokine which has direct vasorelaxant effects on vascular smooth muscle cells (VSMC). In the present study, IL-1 markedly increased intracellular levels of the vasodilatory mediator, cAMP, in human saphenous and human aortic VSMC. IL-1 induced cAMP was associated with a marked increase in prostacyclin (PGI2) production and was reversed by indomethacin and tranylcypromine, inhibitors of cyclooxygenase and PGI2 synthetase respectively. Furthermore, PGI2, but not PGE2, was a potent inducer of cAMP production in HSVSMC, implicating a role for PGI2 in mediating IL-1-induced cAMP production. In previous studies, IL-1 increased immunoreactive cGMP production in human saphenous VSMC through a pathway inhibitable by soluble guanylate cyclase inhibitors, methylene blue and LY83583, but not by nitric oxide (NO) synthase inhibitors, suggesting a role of NO-independent activation of soluble guanylate cyclase. However, in the present study, it was found that cAMP cross-reacted significantly in cGMP radioimmunoassays employing three out of four commercial antisera, that IL-1 did not affect cGMP production in human saphenous or human aortic VSMC as determined by an RIA having low cAMP cross-reactivity, and that both LY83583 and methylene blue inhibited IL-1 induced increases in cAMP. The results implicate prostacyclin-dependent cAMP production as a mediator of the vasodilatory effects of IL-1 in humans.