Peroxisome proliferator-activated receptor-gamma is expressed by rat peritoneal mesothelial cells: its potential role in peritoneal cavity local defense.
OBJECTIVE
Peritoneal mesothelial cells (PMCs) play an important role in peritoneal inflammatory and immune response. It was reported that the peroxisomal proliferator-activated receptor-gamma (PPARgamma) ligand could effectively reduce inflammatory processes. However, the expression and function of PPARgamma in PMCs has not been reported. This study was to investigate the expression of PPARgamma in rat PMCs and the effect of PPARgamma 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-PGJ(2), and ciglitazone at different time points. The mRNA and protein expression of PPARgamma, CD40 and ICAM-1 were detected by RT-PCR and Western blot, respectively. The intracellular distribution of PPARgamma was detected by immunocytochemistry.


RESULTS
RPMCs expressed PPARgamma both at the mRNA and protein level. The specific signals for PPARgamma 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 PPARgamma with the peak of mRNA at 3 h and protein at 12 h. Thereafter the expression of PPARgamma gradually attenuated. The mRNA expressions for CD40, ICAM-1 and protein expression of ICAM-1 were significantly upregulated following stimulation with LPS. Both 15d-PGJ(2) and ciglitazone decreased the expression of CD40 mRNA and ICAM-1 protein. However, ciglitazone was less effective than 15d-PGJ(2).


CONCLUSIONS
There is constitutive expression of PPARgamma in cultured RPMCs and PPARgamma ligands which strongly inhibit LPS-induced CD40 and ICAM-1 production in RPMCs. It suggested that PPARgamma 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.
Zhang
Yun Fang
YF
Department of Nephrology, 1st Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Yang
Xiao
X
Zhang
Ya Jie
YJ
Sun
Yu Ling
YL
Zou
Xun Liang
XL
Kong
Qing Yu
QY
Dong
Xiu Qing
XQ
Ye
Xiao Qing
XQ
Yu
Xue Qing
XQ
D000818:Animals; D019013:CD40 Antigens / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D047495:PPAR gamma / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D010537:Peritoneum / Q000276:immunology / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D019013:CD40 Antigens; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D047495:PPAR gamma; D045162:Thiazolidinediones; D018799:Intercellular Adhesion Molecule-1; D015230:Prostaglandin D2; C039671:ciglitazone