MKP-1 attenuates LPS-induced blood-testis barrier dysfunction and inflammatory response through p38 and IκBα pathways
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Yiqing Pan1, Yue Liu1, Li Wang1, Feng Xue1,2, Yanqin Hu1, Ran Hu3, Chen Xu1
1Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China
2Laboratory of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Chen Xu, email: [email protected]
Keywords: MAP phosphatase-1, occludin, signaling transduction, inflammation, testicular immune privilege
Received: August 02, 2016 Accepted: October 04, 2016 Published: October 22, 2016
Sertoli cells create a local tolerogenic microenvironment to maintain testicular immune privilege especially through the formation of a blood-testis barrier (BTB). However, the molecular mechanisms underlying the immune modulation function and BTB dynamics of Sertoli cells remained elusive. MAP phosphatase (MKP)-1 acts as a crucial negative regulator of the inflammatory response. Nevertheless, the role of MKP-1 in regulating Sertoli cells has not been elucidated. In this study, we have for the first time uncovered distinct cellular localization of MKP-1 in the cells at different stages of mouse testis, and the level of MKP-1 expression was significantly up-regulated by LPS-induced acute testis inflammation. In addition, MKP-1 staining was strongly detected in nuclei and peri-nuclear regions of cytoplasm in the Sertoli cells, and it was presented at Sertoli cell tight junctions (TJs) at stages VII-VIII after LPS treatment. Moreover, we demonstrated that MKP-1 was capable of attenuating LPS-induced decrease of occludin by interaction with p38 MAP kinase and IκBα molecules. Taken together, our data highlight that MKP-1 was an important endogenous suppressor of innate immune responses involved in the regulation of BTB barrier dynamic. This study thus might offer novel targets for treating inflammatory diseases in the testis.
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