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  2. The ERβ-CXCL19/CXCR4-NFκB pathway is critical in mediating the E2-induced inflammation response in the orange-spotted grouper (Epinephelus coioides)

The ERβ-CXCL19/CXCR4-NFκB pathway is critical in mediating the E2-induced inflammation response in the orange-spotted grouper (Epinephelus coioides)

  • J Steroid Biochem Mol Biol. 2021 Sep;212:105926. doi: 10.1016/j.jsbmb.2021.105926.
Qing Wang 1 Fengqi Huang 2 Xuzhuo Duan 2 Huitao Cheng 2 Chunli Zhang 2 Lihua Li 2 Xinhe Ruan 2 Qi He 2 Wenbiao Niu 2 Huirong Yang 2 Danqi Lu 3 Leyun Zheng 4 Huihong Zhao 5
Affiliations

Affiliations

  • 1 College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, Guangzhou, 510642, China.
  • 2 College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
  • 3 State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory for Aquatic Economic Animals and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.
  • 4 Fisheries Research Institute of Fujian, Xiamen, 361000, China.
  • 5 College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, Guangzhou, 510642, China. Electronic address: zhaohh@scau.edu.cn.
Abstract

The main physiological function of 17β-estradiol (E2) in vertebrates is to regulate sexual development and reproduction. In fish, especially hermaphroditic fish, estrogen is often used to aid reproduction, but it also can trigger an inflammatory response. However, the molecular mechanism for this E2-induced inflammatory reaction is not clear. In this study, we found that the ERβ-CXCL19/CXCR4-NFκB cascade regulated the E2-induced inflammatory response in the orange-spotted grouper (Epinephelus coioides). Strikingly, E2 treatment resulted in significantly high expression of inflammatory cytokines and induced phosphorylation and degradation of IκBα and translocation of NFκB subunit p65 to the nucleus in grouper spleen cells. However, the E2-induced inflammatory response could be prevented by the broad Estrogen Receptor (ER) ligand ICI 182,780. Moreover, the luciferase assay showed that E2 induced the inflammatory response by activating the promotor of chemokine CXCL19 through ERβ1 and ERβ2. Knockdown of CXCL19 blocked the E2-induced inflammatory response and NFκB nucleus translocation. Additionally, knockdown of chemokines CXCR4a and CXCR4b together, but not alone, blocked the E2-induced inflammatory response. The immunofluorescence assay and co-immunoprecipitation analysis showed that CXCL19 mediated the E2-induced inflammatory response by activating CXCR4a or CXCR4b. Taken together, these results showed that the ERβ-CXCL19/CXCR4-NFκB pathway mediated the E2-induced inflammatory response in grouper. These findings are valuable for future comparative immunological studies and provide a theoretical basis for mitigating the adverse reactions that occur when using E2 to help fish reproduce.

Keywords

17β-estradiol; Chemokine; Grouper; Inflammatory; Signal pathway.

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