Peroxisome Proliferator-Activated Receptor-Gamma Is Expressed by Rat Peritoneal Mesothelial Cells: Its Potential Role in Peritoneal Cavity Local Defense

Abstract

Background/Aims: Peritoneal mesothelial cells (PMCs) play an important role in peritoneal inflammatory and immune response. It was reported that the peroxisomal proliferator-activated receptor-γ (PPARγ) ligand could effectively reduce inflammatory processes. However, the expression and function of PPARγ in PMCs has not been reported. This study was to investigate the expression of PPARγ in rat PMCs and the effect of PPARγ activation on the production of CD40 and ICAM-1 induced by lipopolysaccharide (LPS). Methods: Rat PMCs (RPMCs) were harvested from the peritoneal cavity of Sprague-Dawley rats and maintained under defined in vitro conditions. The cells were treated separately with LPS, 15d-PGJ₂, and ciglitazone at different time points. The mRNA and protein expression of PPARγ, CD40 and ICAM-1 were detected by RT-PCR and Western blot, respectively. The intracellular distribution of PPARγ was detected by immunocytochemistry. Results: RPMCs expressed PPARγ both at the mRNA and protein level. The specific signals for PPARγ were mainly localized in the nucleus with weak staining in the cytoplasm. Stimulation of RPMCs with LPS resulted in a time-dependent increase in the expression of PPARγ with the peak of mRNA at 3 h and protein at 12 h. Thereafter the expression of PPARγ gradually attenuated. The mRNA expressions for CD40, ICAM-1 and protein expression of ICAM-1 were significantly upregulated following stimulation with LPS. Both 15d-PGJ₂ and ciglitazone decreased the expression of CD40 mRNA and ICAM-1 protein. However, ciglitazone was less effective than 15d-PGJ₂. Conclusions: There is constitutive expression of PPARγ in cultured RPMCs and PPARγ ligands which strongly inhibit LPS-induced CD40 and ICAM-1 production in RPMCs. It suggested that PPARγ might play a part in the local defense of the peritoneal cavity by downregulating inflammatory mediators, which may play a potential role in preventing peritoneal fibrosis induced by peritonitis. Further in vivo study is needed to demonstrate the long-term effects.