Identification and regulation of testicular interferon gamma (IFN-g) receptor subunits: IFN-g enhances interferon regulatory factor-1 (IRF-1) and interleukin-1b-converting enzyme (ICE) expression and susceptibility to genistein-induced apoptosis
Kanzaki,Masanori; Morris,Patricia L.
Endocrinology 139(5): 2636-2644
Publication date: 1998
Interferon- (IFN) transmits its signal through a specific cell surfacereceptor (IFNR), which consists of a primary ligand binding -chain(IFNR) and a signaling ß-chain (IFNRß). Recent studiesidentified the cytokines IFN, interleukin-6 (IL-6), IL-1, andtumor necrosis factor- in testicular cells. Therefore, we: 1) examinedthe expression of IFNR and IFNRß subunits in freshly isolatedand purified rat testicular cells; 2) examined the differentialregulation of receptor components by cytokines using primarycultures of Sertoli cells; 3) identified the cell signaling pathwaycomponents of testicular IFNR; and 4) characterized the functionalrole of testicular IFN using primary Sertoli cells. We demonstratedthe messenger RNAs for both chains of IFNR in rat testicularcells using Northern hybridization analysis. Western blot analysisand immunocytochemistry showed that both specific IFNR proteinsubunits were present in cultured primary Leydig and Sertoli cellsprepared from the testes of immature rats. The expression ofboth IFNR component messenger RNAs in cultured Sertoli cellswas increased by its specific ligand (IFN), as well as IL-1and tumor necrosis factor-, in both a time- and dose-dependentmanner. IFN-activation of the Janus (JAK) tyrosine kinases,JAK1 and JAK2 proteins, indicate that IFNR, expressed in theSertoli cell, is functional. Moreover, IFN modulates the expressionof interferon regulatory factor (IRF)-1 and IL-1ß convertingenzyme genes in Sertoli cells. Thus, our data are suggestiveof a role(s) for IFN- in the regulation of distinct gene expressionand cell-specific sensitivity to apoptosis in the testis.