PMID: 8614032Apr 1, 1996Paper

Prostaglandin E2 production by endotoxin-stimulated alveolar macrophages is regulated by phospholipase C pathways

The Journal of Trauma
C J LoR V Maier

Abstract

Eicosanoids play an important role in many aspects of systemic inflammatory responses and host defense. Although the synthesis of eicosanoids by different enzymes has been elucidated, the regulatory mechanism of eicosanoid production is not clear. We designed this study to investigate the hypothesis that PGE2 production by endotoxin (lipopolysaccharide; LPS)-stimulated macrophages (MO) is dependent on phospholipase C (PLC) signaling pathways. Rabbit alveolar macrophages (MO) were obtained by bronchoalveolar lavage. MO were suspended in RPMI-1640 medium at 1 x 10(6)/mL and were exposed to Escherichia coli LPS (10 ng/mL) +/- various agonists and antagonists of PLC and its secondary messengers. After 24 hours of incubation, prostaglandin E2 (PGE2) production was measured by ELISA. LPS-activated MO produced four times as much PGE2 as did control unstimulated MO. The increase in PGE2 production was inhibited by PLC inhibitors (U73122 or D609) and a low-molecular-weight PLA2 inhibitor, manoalide. An increase in intracellular calcium and activation of both the calmodulin and protein kinase C kinase pathways increase PGE2 production. PGE2 production is intimately dependent on several phospholipases. Production is not only dependent on ...Continue Reading

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Citations

Oct 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D HarryK Moore
Jun 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M MayneJ D Geiger
Jun 16, 2010·Pharmacology & Therapeutics·Ashiwel S Undieh

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