mPGES-1 is considered an alternative target for anti-inflammatory treatment with improved selectivity and safety compared to NSAIDs. mPGES-1 depletion not only suppresses inflammation via absence of inducible PGE2 but might also cause an activation of anti-inflammatory pathways. We studied effects of mPGES-1 deletion on the eicosanoid and fatty acid (FA) profiles in mice. In LPS-induced peritoneal macrophages from mPGES-1 knock-out (mPGES-1-/-, KO) mice PGE2 production was markedly attenuated, whereas levels of PGD2 metabolites (15-deoxy-Δ(12,14) PGJ2 and 15-deoxy-Δ(12,14) PGD2) were increased compared to wild type mice. The levels of oxidized fatty acid 13-HODE were also significantly up-regulated in KO macrophages. Significant differences in the total lipid FA composition (decrease in monounsaturated FA and increase in eicosadienoic acid) were detected in spleen of KO and WT mice. These effects of mPGES-1 deletion on eicosanoid and fatty acid metabolism have important implications for future mPGES-1 inhibitors and deserve further investigation.
Keywords: Eicosanoids; Fatty acids; Inflammation; Knock-out mice; Prostaglandins E(2); mPGES-1.
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