Testosterone attenuates pulmonary epithelial inflammation in male rats of COPD model through preventing NRF1-derived NF-κB signaling  

作　　者：Xueting Wang Linlin Huang Shan Jiang Kang Cheng Dan Wang Qianqian Luo Xiaomei Wu Li Zhu 

机构地区：[1]Institute of Special Environmental Medicine,Nantong University,Nantong 226019,China

出　　处：《Journal of Molecular Cell Biology》2021年第2期128-140,共13页分子细胞生物学报（英文版）

基　　金：The study was supported by grants from the National Natural Science Foundation of China(31671206,81702874,81873924,and 81971131).

摘　　要：Testosterone deficiency is common in male patients with chronic obstructive pulmonary disease (COPD) and may correlate with the deterioration of COPD. Clinical research suggests that testosterone replacement therapy may slow the COPD progression, but the specific biological pathway remains unclear. In this study, we explored the effect of testosterone on pulmonary inflammation in male COPD rats. The animals were co-treated with lipopolysaccharide (LPS) and cigarette to induce COPD. In COPD rats, nuclear respiratory factor 1 (NRF1) and NF-κB p65 were upregulated. In cigarette smoke extract (CSE)-, LPS-, or the combination of CSE and LPS-treated L132 cells, NRF1 and p65 were also upregulated. Silencing NRF1 resulted in the downregulation of p65. ChIP‒seq, ChIP‒qPCR, and luciferase results showed that NRF1 transcriptionally regulated p65. Both male and female COPD rats showed an upregulated NRF1 level and similar pulmonary morphology. But NRF1 was further upregulated in male castrated rats. Further supplementing testosterone in castrated male rats significantly reduced NRF1, pulmonary lesions, and inflammation. Supplementation of testosterone also reduced the phosphorylation of p65 and IKKβ induced by LPS or CSE in L132 cells. Our results suggest that testosterone plays a protective role in pulmonary epithelial inflammation of COPD through inhibition of NRF1-derived NF-κB signaling and the phosphorylation of p65.

关 键 词：testosterone replacement therapy COPD NRF1 NF-ΚB transcriptional regulation ENDOTHELIA 

分 类 号：R563[医药卫生—呼吸系统]