[PubMed] [Google Scholar] 37
[PubMed] [Google Scholar] 37. This study thus might offer novel targets for treating inflammatory diseases in the testis. hybridization [16]. Furthermore, 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]. However, it remains unknown about the role of MKP-1 in the seminiferous tubules during pathogen infection. Additionally, the mechanisms in which signaling pathway molecules participate remain to be defined. Sertoli cells, the only somatic cell type within the seminiferous tubules, play a critical role in controlling testicular immune privilege status and local defense responses [19]. It has been demonstrated that Sertoli cells not only serve as a WNK-IN-11 physical wall (by creating the BTB) but also possess the capacity to modulate the immune response [20, 21]. Furthermore, there are several excellent studies showing that MAP kinase pathway plays an important role in numerous male reproductive processes, including BTB dynamics, the germ cell-cycle progression and differentiation, and germ cell apoptosis in the seminiferous epithelium [22, 23]. On the other hand, some studies suggest that MAP kinase pathway is often involved in male reproductive dysfunction in some infection status [24]. Since activation of MAPK is associated with transduction downstream signals in the control of male reproductive processes, the inactivation of the MAPK is the same importance as its activation [25]. ZCYTOR7 Consequently, it is of great significance to probe the role of MKP-1 in seminiferous epithelium, particularly, the immunological and physiological function of MKP-1 on BTB dynamic changes in infection status. Occludin is the first identified integral membrane protein in the tight junction (TJ) [26], which plays an important role for proper TJ function in spermatogenesis [27C30]. Recent studies have shown that focal adhesion kinase (FAK) is structurally associated with occludin and regulates the structural interaction between occludin and ZO-1 in primary Sertoli cells [31]. In line with this regulatory mechanism, occludin has been indicated to serve as a substrate for a wide range of kinases and phosphatases in various pathophysiological contexts, illustrating that occludin may act as a signaling regulatory TJ protein [32]. In addition, it is interesting to note that BTB dysfunction is associated with activation of the MAP kinase pathway [22C24]. Although WNK-IN-11 there is a general appreciation with the role of signaling pathway in the integrity of the BTB and the homeostasis of the seminiferous epithelium, it remains unclear how Sertoli cells contribute to creating a local tolerogenic environment by WNK-IN-11 BTB and modulation of the immune response during pathogen infection. Therefore, this study was designed to elucidate the immune modulation function of MKP-1 in BTB dynamic especially on infection status. In the present study, the expression pattern of MKP-1 was studied after LPS-induced acute testis inflammation. We revealed that induction of MKP-1 was correlated with the inactivation of MAP kinases and IB molecules in the LPS-stimulated Sertoli cells, suggesting that MKP-1 is a key endogenous suppressor of innate immune responses on testis infection status. We also identified that MKP-1 was capable of attenuating LPS-induced down-regulation of occludin by interaction with p38 MAP kinase and IB molecules. These results presented a novel mechanism of MKP-1 in modulating BTB dynamic. In addition, our findings may represent a novel mechanism for understanding the precise physiological relationship between immune regulation.