title: Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis.
abstract: Dysfunction in macrophage-mediated phagocytosis of aberrant cells that undergo retrograde transport to the peritoneal cavity is considered an important factor in the development of endometriosis. However, the mechanisms responsible for the loss of function of macrophages remain largely unknown. Herein, we report that prostaglandin (PG) E(2), via the EP2 receptor-dependent signaling pathway, inhibits the expression of CD36 in peritoneal macrophages, resulting in reduced phagocytic ability. PGE(2)-mediated inhibition of macrophage phagocytic capability was restored by ectopic expression of CD36. Treatment with PGE(2) inhibited CD36-dependent phagocytosis of peritoneal macrophages and increased the number and size of endometriotic lesions in mice. In contrast, blockade of PGE(2) production by cyclooxygenase inhibitors enhanced the phagocytic ability of peritoneal macrophages and reduced endometriotic lesion formation. Taken together, our findings reveal a potential mechanism of immune dysfunction during endometriosis development and may contribute to the design of an effective prevention/treatment regimen.
authors.affiliation: Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China.
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Chuang
authors.forename: Yiu-Juian
authors.initials: YJ
authors.lastname: Lin
authors.forename: Meng-Hsing
authors.initials: MH
authors.lastname: Wu
authors.forename: Lih-Yuh C
authors.initials: LY
authors.lastname: Wing
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shoji
authors.forename: Shaw-Jenq
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects; D004715:Endometriosis / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010532:Peritoneal Diseases / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D058307:Receptors, Prostaglandin E, EP2 Subtype; D020298:U937 Cells
chemical_list: D018955:CD36 Antigens; C545644:PTGER2 protein, human; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015232:Dinoprostone