Elsevier

Nitric Oxide

Volume 6, Issue 3, May 2002, Pages 255-262
Nitric Oxide

Regular Article
Role of Ca2+-Independent Phospholipase A2 and Cyclooxygenase/Lipoxygenase Pathways in the Nitric Oxide Production by Murine Macrophages Stimulated by Lipopolysaccharides

https://doi.org/10.1006/niox.2001.0410Get rights and content

Abstract

There is evidence of molecular cross talk between inflammatory mediators such as nitric oxide (NO) and prostaglandins (PG), which may regulate tissue homeostasis and contribute to pathophysiological processes. Here we examine the role of endogenous arachidonic acid (AA) and its AA metabolites in the regulation of NO release by lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. Our results suggest that bromoenol lactone-sensitive phospholipase A2 is involved in AA release and the subsequent PG and leukotriene (LT) production. The cyclooxygenase inhibitor, indomethacin, and lipoxygenase inhibitors such as baicalein and zileuton blocked the dose-dependent PGE2 or LTB4 and nitrite (NO2) production induced by LPS. Furthermore, the effects of indomethacin were reverted by exogenous PGE2 and forskolin, whereas AH23848B, an EP4 PGE2 subtype receptor antagonist, decreased NO2 release. On the other hand, the effect of baicalein on NO2 production was reverted by exogenous LTB4 and the fibrate WY 14,643, a natural and a synthetic peroxisome proliferator-activated receptor α (PPARα), respectively. Thus, PGE2 via EP4 receptor/cAMP and LTB4 via PPARα may be involved in the control of NO synthesis by LPS in macrophage RAW 264.7 cultures.

References (38)

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