S Sawatsri1, N Desai, J A Rock, N Sidell. 1. Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Abstract
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.
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.
Authors: Keely Pierzchalski; Robert N Taylor; Ceana Nezhat; Jace W Jones; Joseph L Napoli; Guixiang Yang; Maureen A Kane; Neil Sidell Journal: Biol Reprod Date: 2014-08-20 Impact factor: 4.285
Authors: Neil Sidell; Yue Feng; Lijuan Hao; Juanjuan Wu; Jie Yu; Maureen A Kane; Joseph L Napoli; Robert N Taylor Journal: Mol Endocrinol Date: 2009-11-12