Department of Gynecology and Obstetrics, Emory Center for Advanced Research on Women's Health, Emory University, Atlanta, Georgia 30322, USA
Address for correspondence: Neil Sidell, Ph.D., Department of Gynecology and Obstetrics, 4303 Woodruff Memorial Research Building, 1639 Pierce Drive, Emory University School of Medicine, Atlanta, GA 30322. Voice: 404-727-9155; fax: 404-727-8615.
nsidell{at}emory.edu
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 NF
B, 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 PPAR
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.
