Uterine chemokines in reproductive physiology and pathology

PROBLEM: Chemokines are increasingly recognized as important regulators of uterine function. METHODS OF STUDY: The following is a review of uterine chemokines, especially monocyte chemotactic protein (MCP)-1, interleukin (IL)-8, and regulated-upon-activation normal-T-cell-expressed and -secreted (RANTES) protein, in reproductive physiology and pathology. RESULTS: It is increasingly clear that IL-8, MCP-1, RANTES and their receptors are produced by endometrial, myometrial, and trophoblast cell types in a timed and co-ordinated manner. In addition to the regulation of leukocyte migration and function, uterine chemokines also display specific roles in endometrial angiogenesis, apoptosis, proliferation, and differentiation. IL-8, MCP-1 and RANTES are regulated by local growth factors and cytokines such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and IL-1. IL-8 takes part in cervical ripening and parturition. IL-8, MCP-1 and RANTES are also found at high levels in the peritoneal fluid of women with endometriosis. CONCLUSION: Co-ordination of chemokine-chemokine receptor interactions plays an important role in the menstrual cycle and successful pregnancy. Moreover, unbalanced chemokine expression contributes to pathologic conditions typified by uncontrolled cellular proliferation, migration and invasion.