Objective: To determine whether retinoic acid (RA) can regulate the express
ion 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 exp
ression, and IL-6-promoter activity,
Result(s): Using a human endometrial cell line (EM42), as well as primary s
tromal and epithelial endometrial cells, we demonstrated that RA suppresses
IL-6 protein and messenger RNA expression in a time- and dose-dependent fa
shion, 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 tr
ansfected into EM42 cells. Mutational analysis of reporter constructs indic
ated 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 pathophys
iology of endometriosis related to aberrant production of IL-6, (Fertil Ste
ril(R) 2000;73:1012-9. (C) 2000 by American Society for Reproductive Medici
ne).