Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing effects on monocyte chemotaxis in endometriosis

The peroxisome proliferator-activated receptors (PPARs) alpha and gamma are nuclear receptors that play important roles in inflammatory diseases like ulcerative colitis and arthritis. In this study,we examined the possible ro le of PPARs in macrophage attraction into the peritoneal cavity of patients with endometriosis. We identified PPAR-alpha and gamma messenger RNA by RT -PCR and protein by immunoblotting of lysates of peritoneal macrophages and monocytic:U937 cells. Using immunocytochemistry, we localized PPAR-alpha a nd -gamma within the nuclei of both cell types. monocyte chemotactic activi ty of peritoneal fluid from patients with endometriosis was quantified in B oyden chambers. Migration of U937 cells was increased by WY 14643 and reduc ed by rosiglitazone. Peritoneal fluid from patients with endometriosis acti vated U937 cells transiently transfected with a PPAR-alpha /GAL4 luciferase reporter. By contrast, peritoneal fluid did not cause significant activati on of PPAR-gamma /GAL4 constructs. The U937 cells transiently transfected w ith a PEAR response element luciferase reporter showed disease stage-depend ent up-regulation when treated with peritoneal fluid from patients with end ometriosis. Treatment with peritoneal fluid from healthy controls down-regu lated PPAR response element transactivation. We conclude that peritoneal fl uid of endometriosis patients contains activators of PPAR-alpha that stimul ate macrophage chemotaxis. Inhibitors of PPAR-alpha or activators of PPAR-g amma could be developed for the treatment of inflammation associated with e ndometriosis.