Curcumin suppresses an endometrial cell inflammation through inhibition of SREBP-1

Abstract

Curcumin is a natural polyphenolic compound extracted from the spice, turmeric and has been reported to evidence anti-inflammatory, antioxidant, and antiproliferative properties via the modulation of multiple cellular mechanisms. Endometriosis, the presence of ectopic endometrial tissue outside the uterine cavity, is a common disease affecting women during their reproductive years. In this study, we showed the effects of curcumin on endometrial cell inflammation. Curcumin inhibited expression of cyclooxygenase-2, which is a pivotal player in inflammatory processes, in the endometrium cells by using luciferase assays, real-time PCR and Western blotting analyses. Furthermore, curcumin exerted inhibitory effects via NF-κB-dependence in part. Decrease of inflammatory gene expression by curcumin in ovary cells was mediated by inhibition of transcription factor SREBP-1 and Akt signaling. In conclusion, the results indicate that curcumin may be potentially useful as novel anti-inflammatory reagents when administered in endometriosis. Introduction There is general agreement that endometriosis is a chronic pelvic inflammatory process, characterized by enhanced numbers of activated peritoneal immune cells and pro-inflammatory factors [1,2]. In particular, increased concentrations of prostaglandins (PGs) and leukotrienes have been found in the peritoneal fluid of endometriosis patients [3]. These are the major constituents of a group of biologically active oxygenated fatty acids known as eicosanoids and have been implicated in various inflammatory diseases. In endometriosis, they appear to play an important role in disease-associated pain, essentially treated with non-steroidal anti-inflammatory drugs [4]. These inflammatory mediators, particularly PGs, may also be directly involved in the pathogenesis of endometriosis, as recent in vitro studies have demonstrated that improved synthesis is involved in enhancing proliferation while inhibiting apoptosis, increasing both angiogenesis and immunosuppression [5]. The cyclooxygenase (COX) pathway leads to the formation of PGs. Curcumin is a natural polyphenolic compound extracted from the spice, turmeric and has been reported to evidence anti-inflammatory, antioxidant, and anti-proliferative properties via the modulation of multiple cellular [6]. However, it remains to be determined whether curcumin affects in the process of endometriosis. The evolution of hepatic inflammation is controlled by specific transcriptional regulators, some of which are well known in the context of cholesterol-inducible inflammation (SREBPs, NF-κB, AP-1, C/EBPs) [7]. Interestingly, some of these factors may also represent molecular links between lipid/cholesterol metabolism and inflammation. Considering that SREBP-1 can promote inflammation and be regulated by hypoxia, we showed that low cellular oxygen tension in endometriotic stromal cells up-regulated SREBP1 expression *Correspondence to: JaeHun Cheong, Department of Molecular Biology, Pusan National University, Busan, 609-735, Korea, Tel: 82-51-510-2277; Fax: 82-51513-9258; E-mail: molecule85@pusan.ac.kr