Peroxisome proliferator-activated receptor β/δ (PPARβ/δ), a ligand-activated nuclear receptor, regulates lipid and glucose metabolism and inflammation. PPARβ/δ can exert an anti-inflammatory effect by suppressing proinflammatory cytokine production. Cyclooxygenase-2 (COX-2)-triggered inflammation plays a crucial role in the development of many inflammatory diseases, including glomerulonephritis. However, the effect of PPARβ/δ on the expression of COX-2 in the kidney has not been fully elucidated. The present study showed that PPARβ/δ was functionally expressed in human mesangial cells (hMCs), where its expression was increased by interleukin-1β (IL-1β) treatment concomitant with enhanced COX-2 expression and prostaglandin E2 (PGE2) biosynthesis. The treatment of hMCs with GW0742, a selective agonist of PPARβ/δ, or the overexpression of PPARβ/δ via an adenovirus-mediated approach significantly increased COX-2 expression and PGE2 production. PPARβ/δ could further augment the IL-1β-induced COX-2 expression and PGE2 production in hMCs. Moreover, both PPARβ/δ activation and overexpression markedly increased sirtuin 1 (SIRT1) expression. The inhibition or knockdown of SIRT1 significantly attenuated the effects of PPARβ/δ on the IL-1β-induced expression of COX-2 and PGE2 biosynthesis. Taken together, PPARβ/δ could augment the IL-1β-induced COX-2 expression and PGE2 production in hMCs via the SIRT1 pathway. Given the critical role of COX-2 in glomerulonephritis, PPARβ/δ may represent a novel target for the treatment of renal inflammatory diseases.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320509PMC
http://dx.doi.org/10.3390/metabo12070595DOI Listing

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