The aim of this study was to investigate the possible relationship between prostaglandin (PG) and nitric oxide (NO) biosynthetic pathways in human amnion-like WISH cells. Our results indicate that: (1) sodium nitroprusside (SNP), a NO donor, dose-dependently increases spontaneous prostaglandin E2 (PGE2) release while it inhibits the prostanoid output induced by the inflammatory cytokine, interleukin-1beta (IL-1beta); (2) L-arginine, the substrate of nitric oxide synthase (NOS), is ineffective in both conditions; (3) IL-1beta, which greatly enhances mRNA expression for cyclooxygenase (COX)-inducible isoform (COX-2), does not modify the mRNA expression for the NOS-inducible (iNOS) isoform; (4) indomethacin, which as expected inhibits both basal and IL-1beta-induced PGE2 release, permits the expression of iNOS mRNA in the presence of the cytokine; (5) a similar permissive action on IL-1beta action is exerted by the synthetic steroid betamethasone, which is able to inhibit both mRNA COX-2 expression and IL-1beta-induced PGE2 output in WISH cells; (6) exogenous PGE2 inhibits iNOS mRNA expression induced by indomethacin plus IL-1beta treatment; and (7) PGE2 significantly increases intracellular adenosine 3',5'-cyclic monophosphate (cAMP). The results reported here suggest the existence of a relationship between the prostaglandinergic and nitridergic pathways in WISH cells. In particular, we demonstrate that exogenous NO inhibits PGE2 release evoked by IL-1beta whereas high levels of the prostanoid, in the presence of proinflammatory agents, exert a negative feed-back control on iNOS mRNA expression, possibly through a cAMP-dependent mechanism.
Interactions between the nitric oxide and prostaglandin E2 biosynthetic pathways in human amnion-like WISH cells.
PAVAN, Barbara;VESCE, Fortunato
2003
Abstract
The aim of this study was to investigate the possible relationship between prostaglandin (PG) and nitric oxide (NO) biosynthetic pathways in human amnion-like WISH cells. Our results indicate that: (1) sodium nitroprusside (SNP), a NO donor, dose-dependently increases spontaneous prostaglandin E2 (PGE2) release while it inhibits the prostanoid output induced by the inflammatory cytokine, interleukin-1beta (IL-1beta); (2) L-arginine, the substrate of nitric oxide synthase (NOS), is ineffective in both conditions; (3) IL-1beta, which greatly enhances mRNA expression for cyclooxygenase (COX)-inducible isoform (COX-2), does not modify the mRNA expression for the NOS-inducible (iNOS) isoform; (4) indomethacin, which as expected inhibits both basal and IL-1beta-induced PGE2 release, permits the expression of iNOS mRNA in the presence of the cytokine; (5) a similar permissive action on IL-1beta action is exerted by the synthetic steroid betamethasone, which is able to inhibit both mRNA COX-2 expression and IL-1beta-induced PGE2 output in WISH cells; (6) exogenous PGE2 inhibits iNOS mRNA expression induced by indomethacin plus IL-1beta treatment; and (7) PGE2 significantly increases intracellular adenosine 3',5'-cyclic monophosphate (cAMP). The results reported here suggest the existence of a relationship between the prostaglandinergic and nitridergic pathways in WISH cells. In particular, we demonstrate that exogenous NO inhibits PGE2 release evoked by IL-1beta whereas high levels of the prostanoid, in the presence of proinflammatory agents, exert a negative feed-back control on iNOS mRNA expression, possibly through a cAMP-dependent mechanism.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
