Abstract
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.
Highlights
Testis is an immune-privileged organ that protects auto-antigens from detrimental immune response and counteraction of invading microbial pathogens [1]
Our previous data demonstrated that downregulation of occludin by LPS stimuli in Sertoli cells was more dependent on p38 Mitogen-activated protein kinase (MAPK) and IκBα molecules, and we explored the molecular mechanisms of MKP-1 induction in regulating of occludin
The present study demonstrated the first evidence showing the expression pattern of MKP-1 during LPS-induced acute testis inflammation
Summary
Testis is an immune-privileged organ that protects auto-antigens from detrimental immune response and counteraction of invading microbial pathogens [1]. MKP-1, the first defined member of MKPs [8], has been regarded as an important regulator of innate immune response and tumorigenesis by deactivating both MAP kinases and NFκB pathway in immune cells [9,10,11,12,13,14,15]. It has been demonstrated that MKPs act as a negative regulator to modulate steroidogenesis in MA-10 Leydig cells In these studies, the modulations of ERK1/2 MAP kinase signaling by MKPs on the hormonal action in Leydig cells were explored [17, 18]. The modulations of ERK1/2 MAP kinase signaling by MKPs on the hormonal action in Leydig cells were explored [17, 18] It remains unknown about the role of MKP-1 in the seminiferous tubules www.impactjournals.com/oncotarget during pathogen infection. The mechanisms in which signaling pathway molecules participate remain to be defined
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