Liu Xiaozhen, Nie Shaoping, Huang Danfei, Xie Mingyong
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
Environ Toxicol. 2015 Sep;30(10):1144-52. doi: 10.1002/tox.21987. Epub 2014 Mar 28.
The aim of this study was to investigate the signaling pathways involved in the cyclooxygenase (COX)-2 regulation induced by nonylphenol (NP) in mouse testis Sertoli TM4 cells. Our results showed that treatment of TM4 cells with NP increased COX-2 protein expression and interleukin-6 (IL)-6 and prostaglandin E2 (PGE2) secretion in a dose-dependent manner. Pretreatment with reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC), attenuated NP-induced ROS production, COX-2 expression, and IL-6 and PGE2 release in TM4 cells. Exposure to NP stimulated activation of NF-κB, whereas the NF-κB inhibitor, pyrrolidine dithiocarbamate, attenuated NP-enhanced COX-2 expression and IL-6 and PGE2 release in TM4 cells in a dose-dependent manner. Furthermore, NAC blocked NP-induced activation of NF-κB. In addition, inhibition of COX-2 mitigated NP-induced IL-6 release. In conclusion, NP induced ROS generation, activation of NF-κB pathway, COX-2 upregulation, and IL-6 and PGE2 secretion in TM4 cells. NP may regulate COX-2 expression via ROS-activated NF-κB pathway in Sertoli TM4 cells.
本研究旨在探究壬基酚（NP）诱导小鼠睾丸支持细胞TM4中环氧合酶（COX）-2表达的信号通路。我们的结果显示，用NP处理TM4细胞会以剂量依赖的方式增加COX-2蛋白表达、白细胞介素-6（IL）-6和前列腺素E2（PGE2）的分泌。用活性氧（ROS）清除剂N-乙酰半胱氨酸（NAC）预处理可减弱NP诱导的TM4细胞中ROS产生、COX-2表达以及IL-6和PGE2释放。暴露于NP会刺激核因子κB（NF-κB）的激活，而NF-κB抑制剂吡咯烷二硫代氨基甲酸盐会以剂量依赖的方式减弱NP增强的TM4细胞中COX-2表达以及IL-6和PGE2释放。此外，NAC可阻断NP诱导的NF-κB激活。另外，抑制COX-2可减轻NP诱导的IL-6释放。总之，NP在TM4细胞中诱导了ROS生成、NF-κB通路激活、COX-2上调以及IL-6和PGE2分泌。NP可能通过ROS激活的NF-κB通路在支持细胞TM4中调节COX-2表达。
