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- W2089668511 abstract "Background mPGES-1 is considered an attractive alternative target for anti-inflammatory treatment with improved selectivity and safety compared to NSAIDs. Genetic deletion or pharmacological inhibition of mPGES-1 activity or expression down-regulate inflammation and pain in experimental models of arthritis. However, a detailed understanding of the molecular mechanisms and pathways affected by deletion/inhibition of mPGES-1 is essential before mPGES-1 inhibitors can safely be applied in the clinics. Objectives To investigate the effect of mPGES-1 deletion on the levels of bioactive lipid mediators such as the eicosanoids (down-stream cascade) and fatty acids (up-stream cascade). Methods Peritoneal macrophages (PM) from wild type (WT) and knock-out (mPGES-1-/-, KO) mice were induced with LPS for 16 h. Cells were harvested for gene expression analysis and supernatants were collected for eicosanoid analysis. Gene expression profiling in WT and KO macrophages was performed using the microarray analysis (Applied Biosystems). Eicosanoid profiling of approximately 30 compounds was performed using LC-MS/MS. Fatty acid composition of total lipids in spleen and brain homogenates of WT and KO mice were determined using GC/FID. Results Microarray analysis revealed that genetic deletion of mPGES-1 affected expression of genes related to lipid metabolism and mainly associated with eicosanoid, fatty acid and phospholipid metabolism, (e.g., Pla1A, Ptgis, Fabp3, Cept1, Comt etc). Compared to WT, mPGES-1 deficient PM displayed a markedly attenuated increase in PGE 2 production upon LPS stimulation, and exhibited significantly increased levels of PGD 2 metabolites such as 15-deoxy-Δ 12,14 PGJ 2 and 15-deoxy-Δ 12,14 PGD 2 (p Conclusions Data reveals that mPGES-1 deficient PMs displayed shunting towards PGD 2 pathway, i.e., towards anti-inflammatory metabolites, upon LPS stimulation compared to WT PMs. Moreover, mPGES-1 depletion alters the fatty acid composition of tissue lipids. These effects of inducible PGE 2 on lipid metabolism have important implications for future mPGES-1 inhibitors and deserve further investigation. Disclosure of Interest None Declared" @default.
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- W2089668511 date "2013-06-01" @default.
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- W2089668511 title "AB0042 Deletion of mpges-1 affects fatty acid composition and eicosanoid profiles in mice" @default.
- W2089668511 doi "https://doi.org/10.1136/annrheumdis-2013-eular.2365" @default.
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