title: Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4.
abstract: Testicular inflammation, including noninfectious inflammatory responses in the testis, may impair male fertility. Mechanisms underlying the initiation of noninfectious testicular inflammation are poorly understood. In the current study, we demonstrate that damaged spermatogenic cell products (DSCPs) induce expression of various inflammatory mediators, including TNF-α, IL-1β, IL-6, and macrophage chemotactic protein 1 (MCP-1), in Sertoli cells. Notably, the DSCP-induced inflammatory gene expression was significantly reduced by knockout Toll-like receptor (TLR)2 or TLR4, and abolished by double knockout TLR2 and TLR4 (TLR2(-/-)TLR4(-/-)). MCP-1 secreted by Sertoli cells after stimulation with DSCPs promotes macrophage migration. We also provide evidence that busulfan-induced spermatogenic cell damages in vivo upregulate TNF-α and MCP-1 expression in Sertoli cells, and facilitate macrophage infiltration into the testis in wild-type mice. These phenomena were not observed in TLR2(-/-)TLR4(-/-) mice. Data indicate that DSCPs induce inflammatory gene expression in Sertoli cells via the activation of TLR2 and TLR4, which may initiate noninfectious inflammatory responses in the testis. The results provide novel insights into the mechanisms underlying damaged spermatogenic cell-induced testicular inflammation.
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Tingting
authors.initials: T
authors.lastname: Deng
authors.forename: Weipeng
authors.initials: W
authors.lastname: Xiong
authors.forename: Peng
authors.initials: P
authors.lastname: Lui
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis; D017077:Culture Media, Conditioned; D015870:Gene Expression; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D017737:Macrophages, Peritoneal / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D009920:Orchitis / Q000378:metabolism; D012708:Sertoli Cells / Q000276:immunology / Q000378:metabolism*; D013093:Spermatogonia / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha