MKP-1 attenuates LPS-induced blood-testis barrier dysfunction and inflammatory response through p38 and IκBα pathways.
MKP-1 attenuates LPS-induced blood-testis barrier dysfunction and inflammatory response through p38 and IκBα pathways.
复制标题
MKP-1 通过 p38 和 IkappaBalpha 途径减弱 LPS 诱导的血睾屏障功能障碍和炎症反应。
DOI：
10.18632/oncotarget.12823
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发表时间：
2016-12-20
期刊：
影响因子：
--
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Pan Y;Liu Y;Wang L;Xue F;Hu Y;Hu R;Xu C
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.
