Curcumin attenuates proangiogenic and proinflammatory factors in human eutopic endometrial stromal cells through the NF-kappa B signaling pathway

• Type of Material: Article
• Authors: Indrajit Chowdhury, Morehouse School of Medicine; Saswati Banerjee, Morehouse School of Medicine; Adel Driss, Morehouse School of Medicine; Wei Xu, Morehouse School of Medicine; Sherifeh Mehrabi, Morehouse School of Medicine; Ceana Nezhat, Emory University; Neil Sidell, Emory University; Robert N. Taylor, University of Utah; Winston E. Thompson, Morehouse School of Medicine
• Language: English
• Date: 2019-05-01
• Publisher: Wiley: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/jcp.27360
• Title of Journal or Parent Work: Journal of Cellular Physiology
• ISSN: 0021-9541
• Volume: 234
• Issue: 5
• Start Page: 6298
• End Page: 6312
• Grant/Funding Information: This investigation was conducted in a facility constructed with support from Research Facilities Improvement Grant #C06 RR18386 from NIH/NCRR.; This study was supported in part by National Institutes of Health Grants 1SC3 GM113751, U01 HD66439, 1R01HD057235, U54 CA118948, HD41749, S21MD000101, and G12‐RR03034.
• Keywords: Cell Biology; stromal cell; CHEMOKINES; SURVIVAL; Science & Technology; QUALITY-OF-LIFE; human; GENE-EXPRESSION; curcumin; Physiology; PATHOGENESIS; DIAGNOSIS; PERITONEAL-FLUID CONCENTRATIONS; AUTOCRINE MANNER; WOMEN; APOPTOSIS; Life Sciences & Biomedicine; endometriosis
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Obstetrics and Gynecology; Biology, Physiology

Abstract

Endometriosis is a chronic gynecological inflammatory disorder in which immune system dysregulation is thought to play a role in its initiation and progression. Due to altered sex steroid receptor concentrations and other signaling defects, eutopic endometriotic tissues have an attenuated response to progesterone. This progesterone-resistance contributes to lesion survival, proliferation, pain, and infertility. The current agency-approved hormonal therapies, including synthetic progestins, GnRH agonists, and danazol are often of limited efficacy and counterproductive to fertility and cause systemic side effects due to suppression of endogenous steroid hormone levels. In the current study, we examined the effects of curcumin (CUR, diferuloylmethane), which has long been used as an anti-inflammatory folk medicine in Asian countries for this condition. The basal levels of proinflammatory and proangiogenic chemokines and cytokines expression were higher in primary cultures of stromal cells derived from eutopic endometrium of endometriosis (EESC) subjects compared with normal endometrial stromal cells (NESC). The treatment of EESC and NESC with CUR significantly and dose-dependently reduced chemokine and cytokine secretion over the time course. Notably, CUR treatment significantly decreased phosphorylation of the IKKα/β, NF-κB, STAT3, and JNK signaling pathways under these experimental conditions. Taken together, our findings suggest that CUR has therapeutic potential to abrogate aberrant activation of chemokines and cytokines, and IKKα/β, NF-κB, STAT3, and JNK signaling pathways to reduce inflammation associated with endometriosis.