You are here

2-dichloroethylethyl sulfide stimulates arachidonic acid metabolism in mouse skin

Title2-dichloroethylethyl sulfide stimulates arachidonic acid metabolism in mouse skin
Publication TypeConference Proceedings
Year of Conference2009
AuthorsHuang M., Gray J.P., Kim H., Casillas R.P., Gerecke D.R, Laskin D.L., Laskin J.D., Heck D.E.
Conference NameProceedings of the Society of Toxicology 48th Annual Meeting and ToxExpo
Date PublishedMarch 15-19, 2009
PublisherSociety of Toxicology
Conference LocationBaltimore, MD

The chemical warfare agent sulfur mustard induces blister formation and severe inflammatory reactions in the skin. In the mouse ear vesicant model (MEVM), sulfur mustard rapidly induces edema and inflammation as well as acanthosis and hypergranulosis. In previous studies we demonstrated that in the MEVM, 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant, rapidly induces the production of the antioxidant heme oxygenase-1, as well as inducible nitric oxide synthase and the proinflammatory mediators IL-1b and IL-6. In the present studies we determined if CEES modulated production of prostaglandins and leukotrienes, two important classes of arachidonic acid-derived proinflammatory lipid mediators. CEES (65 mmoles) induced the biosynthesis of both prostaglandin E2 (PGE2) and leukotriene B4 in the skin. This was associated with increases in mRNA expression of COX-2 and PGE2 synthase, two enzymes mediating production of PGE2. Leukotrienes are derived from arachidonic acid via 5-lipoxygenase (5-LOX); CEES decreased expression of 5-LOX mRNA, but increased expression of 5-LOX activating protein (FLAP), a critical protein upregulating leukotriene biosynthesis. CEES also decreased mRNA for leukotriene A4 hydrolase and leukotriene C4 synthetase, as well as 12-lipoxygenase. Taken together these data show that in the MEVM, CEES modulates both the prostaglandin and leukotriene biosynthetic pathways and generates inflammatory mediators. PGE2 and LTB4 antogonists may be important therapeutics for sulfur mustard-induced tissue injury. Supported by NIH grants CA100994, CA093798, ES004738, ES005022, GM034310, and AR055073.

Theme by Danetsoft and Danang Probo Sayekti inspired by Maksimer