Retinoic acid suppresses interleukin-6 production in human endometrial cells

Objective: To determine whether retinoic acid (RA) can regulate the expression of interleukin (IL)-6 in human endometrial cells in a manner that might be beneficial to women with endometriosis. Design: In vitro study. Setting: Academic medical center. Patient(s): Patients with endometriosis and controls. Intervention(s): Endometrial cell cultures were treated with RA. Main Outcome Measure(s): Interleukin-6 protein secretion, messenger RNA expression, and IL-6-promoter activity. Result(s): Using a human endometrial cell line (EM42), as well as primary stromal and epithelial endometrial cells, we demonstrated that RA suppresses IL-6 protein and messenger RNA expression in a time- and dose-dependent fashion, showing maximal effects at pharmacologically achievable blood serum concentrations (micromoles per liter). Retinoic acid specifically inhibited the activity of IL-6-promoter reporter constructs that were transiently transfected into EM42 cells. Mutational analysis of reporter constructs indicated that RA suppression of IL-6 expression was mediated, at least in part, through the nuclear factor IL-6 binding site located in the IL-6 promoter. Conclusion: Retinoids may play a fundamental role in altering the pathophysiology of endometriosis related to aberrant production of IL-6.