PPARβ/δ Augments IL-1β-Induced COX-2 Expression and PGE2 Biosynthesis in Human Mesangial Cells via the Activation of SIRT1

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

Automated summary

This study revealed that PPAR beta/delta enhances IL-1 beta-induced COX-2 expression and PGE2 production in hMCs via the SIRT1 pathway, providing further insights into the role of PPAR beta/delta in regulating renal inflammatory responses.