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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation.

Authors: Smith, Roger S; Kelly, Rodney; Iglewski, Barbara H; Phipps, Richard P

Published In J Immunol, (2002 Sep 01)

Abstract: Pseudomonas aeruginosa causes lethal lung infections in immunocompromised individuals such as those with cystic fibrosis. The lethality of these infections is directly associated with inflammation and lung tissue destruction. P. aeruginosa produces several acylated homoserine lactones (AHL) that are important in the regulation of bacterial virulence factors. Little is known about the effects of AHLs on human cells. In this work we report that the AHL N-(3-oxododecanoyl) homoserine lactone (3O-C(12)-HSL) from P. aeruginosa induces cyclooxygenase (Cox)-2, a seminal proinflammatory enzyme. When primary normal human lung fibroblasts were exposed to 3O-C(12)-HSL, an 8-fold induction in mRNA and a 35-fold increase in protein for Cox-2 were observed. In contrast, there was no substantial change in the expression of Cox-1. We also demonstrated that the induction of Cox-2 was regulated by 3O-C(12)-HSL activation of the transcription factor NF-kappaB. 3O-C(12)-HSL also stimulated an increase in the newly discovered inducible membrane-associated PGE synthase but had no effect on the expression of the cytosolic PGE synthase. We also demonstrate that 3O-C(12)-HSL stimulated the production of PGE(2). PGE(2) is known to induce mucus secretion, vasodilation, and edema, and acts as an immunomodulatory lipid mediator. We propose that 3O-C(12)-HSL induction of Cox-2, membrane-associated PGE synthase, and PGE(2) likely contributes to the inflammation and lung pathology induced by P. aeruginosa infections in the lung. These studies further reinforce the concept that bacterial AHLs not only regulate bacterial virulence but also stimulate the activities of eukaryotic cells important for inflammation and immune defenses.

PubMed ID: 12193735 Exiting the NIEHS site

MeSH Terms: 4-Butyrolactone/analogs & derivatives; 4-Butyrolactone/chemical synthesis; 4-Butyrolactone/pharmacology*; Cell Line; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone/biosynthesis*; Enzyme Induction/drug effects; Enzyme Induction/genetics; Fibroblasts/drug effects; Fibroblasts/enzymology; Fibroblasts/metabolism*; Fibroblasts/pathology*; Homoserine/analogs & derivatives; Homoserine/chemical synthesis; Homoserine/pharmacology*; Humans; Inflammation/enzymology; Inflammation/metabolism; Inflammation/microbiology; Isoenzymes/biosynthesis*; Isoenzymes/genetics; Lung/drug effects; Lung/enzymology; Lung/metabolism*; Lung/pathology*; Membrane Proteins; NF-kappa B/physiology; Prostaglandin-Endoperoxide Synthases/biosynthesis*; Prostaglandin-Endoperoxide Synthases/genetics; Pseudomonas aeruginosa/pathogenicity*; RNA, Messenger/biosynthesis; Up-Regulation/drug effects; Up-Regulation/genetics; Virulence

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