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.


METHODS
In vitro study.


METHODS
Academic medical center.


METHODS
Patients with endometriosis and controls.


METHODS
Endometrial cell cultures were treated with RA.


METHODS
Interleukin-6 protein secretion, messenger RNA expression, and IL-6-promoter activity.


RESULTS
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.


CONCLUSIONS
Retinoids may play a fundamental role in altering the pathophysiology of endometriosis related to aberrant production of IL-6.
Sawatsri
S
S
Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Desai
N
N
Rock
J A
JA
Sidell
N
N
D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000494:pharmacology*; D000097768:Retinoic Acid Receptor gamma
D015850:Interleukin-6; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C082925:retinoic acid receptor beta