Abstract：
Bacterial infection can induce testicular inflammation and damage male fertility. This paper reveals the role of nuclear receptor subfamily 2 group C member 2 (NR2C2) in macrophage cells in orchitis caused by bacterial endotoxin lipopolysaccharide (LPS) infection.
Bacterial infection and induced inflammation are important causes of male infertility. Here, we described the characteristics of expression and the regulatory role of 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 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.
Bacterial infection and induced inflammation are important causes of male infertility. Here, we described the characteristics of expression and the regulatory role of 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 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.
摘要：
细菌感染和诱发炎症是男性不育的重要原因。这里,我们描述了核受体亚家族2组C成员2（NR2C2）在细菌内毒素LPS感染引起的睾丸炎性损伤中的表达特征和调节作用。我们发现在LPS诱导的小鼠睾丸炎模型中，NR2C2在睾丸中高表达，NR2C2在睾丸巨噬细胞中的表达上调。在体外原代睾丸巨噬细胞和RAW264.7细胞中，RNA干扰Nr2c2基因下调IL-1β和IL-6等炎症因子的表达。此外,巨噬细胞中NR2C2的敲除减轻了巨噬细胞分泌的炎症上清液对精原细胞GC-1SPG细胞增殖的抑制作用。机械上,NR2C2通过与NFκb基因启动子中的DR元件结合激活NF-κB信号并促进炎症的发展。这些数据首先证实了在LPS诱导的细菌感染过程中，NR2C2通过NF-κB途径激活IL-1β和IL-6在睾丸巨噬细胞中发挥促炎作用,从而抑制精原细胞的增殖，损害精子的质量。我们的发现揭示了NR2C2在LPS诱导的睾丸炎性损伤中的重要作用，为治疗细菌感染引起的男性不育提供了新的潜在靶点和分子基础。
