Nonylphenol regulates cyclooxygenase‐2 expression via Ros‐activated NF‐κB pathway in sertoli TM4 cells

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. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1144–1152, 2015.