Cytokine-induced secretion of monocyte chemotactic protein-1 by human endometriotic cells in culture

OBJECTIVE: Local secretion of chemotactic factors could contribute to the attraction of macrophages into the peritoneal cavity of women wiht endometriosis. The purpose of this study was to investigate the ability of endometriotic cells to produce monocyte chemotactic and activating protein-1 in response to interleukin-1β and tumor necrosis factor-α, which are found in elevated levels in the peritoneal fluid of patients with endometriosis. STUDY DESIGN: Cultures of fibroblasts-like and epithelial cells isolated from endometriotic tissue were incubated with different concentrations of cytokines for varying periods of time. The de novo secretion of monocyte chemotactic protein-1 in the culture supernants was analyzed by immunoprecipitation and electrophoresis after metabolic labeling with sulfur 35-labeled cysteine RESULTS: The incubation of endometriotic fibroblast-like cells with interleukin-1β and tumor necrosis factor-α resulted in a time- and dose-dependent release of monocyte chemotactic protein-1 into the culure supernatant. Coincubation of the cells with tumor necrosis factor-α and interferon gamma resulted in a synergistic and dose-dependent increase of the monocyte chemotactic protein-1 secretion, whereas interferon gamma alone had no significant effect. Preliminary results indicate that monocyte chemotactic protein-1 is also produced by endometriotic epithelial cells in response to the same cytokines. CONCLUSIONS: Cytokine-stimulated endometriotic cells synthesize and secrete monocyte chemotactic protein-1 in culture, and they may play a relevant role in the recruitment of macrophages to the peritoneal cavity of patients by the local production of chemotactic factors.