17β-estradiol promotes myeloid-derived suppressor cells functions and alleviates inflammatory bowel disease by activation of Stat3 and NF-κB signalings.

Autor: Li P; Key Laboratory of Cardiovascular Diseases, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China; Affiliated Qingyuan Hospital, The Sixth Clinical Medical School, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, 511518, P.R. China., Chen Y; Key Laboratory of Cardiovascular Diseases, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China., Xiang Y; Key Laboratory of Cardiovascular Diseases, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China., Guo R; Key Laboratory of Cardiovascular Diseases, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China., Li X; Key Laboratory of Cardiovascular Diseases, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China., Liu J; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China. Electronic address: liujxiu@mail.sysu.edu.cn., Zhou Y; Department of Biotechnology, School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China. Electronic address: yuting.zhou@gzhmu.edu.cn., Fu X; Key Laboratory of Cardiovascular Diseases, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China; Affiliated Qingyuan Hospital, The Sixth Clinical Medical School, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, 511518, P.R. China; Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China. Electronic address: fuxiaod@gzhmu.edu.cn.
Jazyk: angličtina
Zdroj: The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2024 Sep; Vol. 242, pp. 106540. Date of Electronic Publication: 2024 May 06.
DOI: 10.1016/j.jsbmb.2024.106540
Abstrakt: Inflammatory bowel disease (IBD) describes a group of clinically common autoimmune diseases characterized by chronic intestinal inflammation, with gender differences in prevalence. Estrogen has been previously shown to exert anti-inflammatory action in IBD development, however, the mechanisms remain obscure. Recent research has revealed that myeloid-derived suppressor cells (MDSCs) play a protective role in IBD pathogenesis. To investigate the molecular mechanisms of estrogen steroid 17β-estradiol (E2) in IBD progression, we established IBD mouse models (DNB-induced) with or without prior ovariectomy (OVX) and E2 implantation. We found that OVX led to worse IBD symptoms and reduced MDSCs frequency, whereas E2 significantly alleviated these effects in vivo. Moreover, in vitro experiments showed that E2 promoted the proliferation and immunosuppressive function of MDSCs through phosphorylation of Stat3 and p65. Mechanistically, E2-mediated Stat3/p65 phosphorylation depends on the interaction between HOTAIR, a long non-coding RNA that are well-known in MDSCs proliferation, and Stat3/p65 respectively. In conclusion, our study revealed that E2 promotes the expansion and immunosuppressive function of MDSCs, and thus diminished the occurrence and development of IBD.
Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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