NR2C2 of macrophages promotes inflammation via NF-κB in LPS-induced orchitis in mice.

Abstract

Bacterial infection and induced inflammation are important causes of male infertility. Here, we described the characteristics of expression and the regulatory role of nuclear receptor subfamily 2 group C member 2 (NR2C2) in testicular inflammatory injury induced by infection with the bacterial endotoxin LPS. We found that NR2C2 was highly expressed in the testes and the expression of NR2C2 was upregulated in testicular macrophages in the LPS-induced mouse orchitis model in vivo. In primary testicular macrophages and RAW264.7 cells in vitro, RNA interference with the Nr2c2 gene downregulated the expression of inflammatory factors such as IL-1β and IL-6. In addition, the knockdown of NR2C2 in macrophages alleviated the inhibitory effect of the inflammatory supernatant secreted by the macrophages on the proliferation of spermatogonia GC-1 SPG cells. Mechanistically, NR2C2 activated NF-κB signaling by binding with DR elements in the promotor of the Nfκb gene and promoted the development of inflammation. These data are the first to confirm that during LPS-induced bacterial infection, NR2C2 plays a proinflammatory role by activating IL-1β and IL-6 via the NF-κB pathway in testicular macrophages, consequently inhibiting the proliferation of spermatogonia and damaging the quality of sperm. Our findings reveal the important role of NR2C2 in testicular inflammatory injury induced via LPS and provide a new potential target and a molecular basis for the treatment of male infertility caused by bacterial infection.