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)
复制标题
ERβ-CXCL19/CXCR4-NFκB 途径对于介导橙色斑点石斑鱼（斜带石斑鱼） E2 诱导的炎症反应至关重要。
DOI：
10.1016/j.jsbmb.2021.105926
复制
发表时间：
2021-06-07
影响因子：
4.1
通讯作者：
Zhao, Huihong
中科院分区：
文献类型：
--
作者：
Wang, Qing;Huang, Fengqi;Zhao, Huihong
17 β-雌二醇（E2）在脊椎动物中的主要生理功能是调节性发育和生殖。在鱼类中，特别是雌雄同体的鱼类，雌激素通常用于帮助繁殖，但它也可以引发炎症反应。然而，这种E2诱导的炎症反应的分子机制尚不清楚。在这项研究中，我们发现ERp-CXCL 19/CXCR 4-NF κ B B级联调节E2诱导的石斑鱼（Epineoparus coioides）炎症反应。引人注目的是，E2处理导致炎性细胞因子的显著高表达，并诱导I κ B α的磷酸化和降解以及NF κ B亚基p65向石斑鱼脾细胞核的易位。然而，广泛的雌激素受体（ER）配体ICI 182，780可以预防E2诱导的炎症反应。此外，荧光素酶测定显示，E2通过ER β 1和ER β 2激活趋化因子CXCL 19的启动子来诱导炎症反应。CXCL 19的敲低阻断了E2诱导的炎症反应和NF κ B B核转位。此外，趋化因子CXCR 4a和CXCR 4 b的共同敲低，而不是单独敲低，阻断了E2诱导的炎症反应。免疫荧光试验和免疫共沉淀分析表明，CXCL 19通过激活CXCR 4a或CXCR 4 b介导E2诱导的炎症反应。综上所述，这些结果表明ER beta-CXCL 19/CXCR 4-NF kappa B途径介导了E2诱导的石斑鱼炎症反应。这些发现对未来的比较免疫学研究很有价值，并为减轻使用E2帮助鱼类繁殖时发生的不良反应提供了理论基础。
The main physiological function of 17 beta-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 ERp-CXCL19/CXCR4-NF kappa B 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 I kappa B alpha and translocation of NF kappa B 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 ER beta 1 and ER beta 2. Knockdown of CXCL19 blocked the E2-induced inflammatory response and NF kappa B 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 ER beta-CXCL19/CXCR4-NF kappa B 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.