Regulation and modulation of abnormal immune responses in endometriosis.
There is ample evidence demonstrating that endometriosis is accompanied by inflammatory reactions in the peritoneum, resulting in abnormal levels of a variety of cytokines and chemokines in the peritoneal fluid. Among the immunological parameters that have been shown to be altered in the peritoneal cavity of women with endometriosis, an increase in the number of activated nonadherent macrophages that show reduced surface expression of scavenger receptors has been observed. The cause-and-effect relationship between aberrant peritoneal macrophage activity and endometriosis is still unknown. We have demonstrated that steroid hormone receptor agonists and antagonists [e.g., retinoids, antiglucocorticoids, ligands to peroxisome proliferator activated receptors (PPARs)] can regulate macrophage functions in ways that could either suppress or stimulate the growth of ectopic endometrial lesions. Our studies include a number of relevant findings: (1) RU486, acting as an antioxidant, can suppress activation of NFkappaB, a nuclear transcription factor that affects the expression of several inflammatory genes such as those for MCP-1, GM-CSF, CSF-1, and various adhesion molecules; (2) IL-6 secretion from a variety of cell types including endometrial cells is inhibited by retinoic acid; and (3) retinoids and PPARgamma ligands can upregulate the expression of scavenger receptors in cells of the monocyte/macrophage lineage. These observations, combined with the possibility that macrophage activity may play a fundamental role in endometriosis, suggest that pharmacologic manipulation of macrophage function may provide a novel mechanism for treating this disease.
Sidell
Neil
N
Department of Gynecology and Obstetrics, Emory Center for Advanced Research on Women's Health, Emory University, Atlanta, Georgia 30322, USA. nsidell@emory.edu
Han
Shou Wei
SW
Parthasarathy
Sampath
S
D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004715:Endometriosis / Q000276:immunology*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D015735:Mifepristone / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D018955:CD36 Antigens; D015850:Interleukin-6; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D015735:Mifepristone; D014212:Tretinoin