Nuclear Peroxisome Proliferator-Activated Receptors α and γ Have Opposing Effects on Monocyte Chemotaxis in Endometriosis

D Hornung, Daniela Hornung, Leslie L. Waite, L L Waite, E A Ricke, Emily A. Ricke, F Bentzien, Frauke Bentzien, D Wallwiener, R N Taylor, Robert N. Taylor
The Journal of clinical endocrinology and metabolism · 2001 · vol. 86(7) , pp. 3108–3114 · doi:10.1210/jcem.86.7.7615 · PMID:11443174 · W2058345568
article OA: bronze CC0 ⤵ 24 in-corpus citations
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Peritoneal fluid from endometriosis patients activates nuclear PPAR-alpha in monocytes, increasing chemotaxis, while PPAR-gamma activation decreases it.

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Abstract

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 role 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 and -gamma within the nuclei of both cell types. Monocyte chemotactic activity of peritoneal fluid from patients with endometriosis was quantified in Boyden chambers. Migration of U937 cells was increased by WY 14643 and reduced by rosiglitazone. Peritoneal fluid from patients with endometriosis activated U937 cells transiently transfected with a PPAR-alpha/GAL4 luciferase reporter. By contrast, peritoneal fluid did not cause significant activation of PPAR-gamma/GAL4 constructs. The U937 cells transiently transfected with a PPAR response element luciferase reporter showed disease stage-dependent up-regulation when treated with peritoneal fluid from patients with endometriosis. Treatment with peritoneal fluid from healthy controls down-regulated PPAR response element transactivation. We conclude that peritoneal fluid of endometriosis patients contains activators of PPAR-alpha that stimulate macrophage chemotaxis. Inhibitors of PPAR-alpha or activators of PPAR-gamma could be developed for the treatment of inflammation associated with endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Chemotaxis Endometriosis Monocytes Receptors, Cytoplasmic and Nuclear Saccharomyces cerevisiae Proteins Transcription Factors Apoptosis Ascitic Fluid Ascitic Fluid Cell Line Cell Nucleus Cell Nucleus DNA-Binding Proteins Endometriosis Female Fungal Proteins Fungal Proteins Humans Immunoblotting Immunohistochemistry

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