Identification and regulation of testicular interferon-γ (IFNγ) receptor subunits:: IFNγ enhances interferon regulatory factor-1 and interleukin-1β converting enzyme expression

Interferon-gamma (IFN gamma) transmits its signal through a specific cell surface receptor (IFN gamma), which consists of a primary ligand binding alpha-chain (IFN gamma R alpha) and a signaling beta-chain (IFN gamma R beta). Recent studies identified the cytokines IFN gamma, interleukin-6 (IL-6), IL-1 alpha, and tumor necrosis factor-or in testicular cells. Therefore, we: 1) examined the expression of IFN gamma R alpha and IFN gamma R beta subunits in freshly isolated and purified rat testicular cells; 2) examined the differential regulation of receptor components by cytokines using primary cultures of Sertoli cells; 3) identified the cell signaling pathway components of testicular IFN gamma R; and 4) characterized the functional role of testicular IFN gamma using primary Sertoli cells. We demonstrated the messenger RNAs for both chains of IFN gamma R in rat testicular cells using Northern hybridization analysis. Western blot analysis and immunocytochemistry showed that both specific IFN gamma R protein subunits were present in cultured primary Leydig and Sertoli cells prepared from the testes of immature rats. The expression of both IFN gamma R component messenger RNAs in cultured Sertoli cells was increased by its specific ligand (IFN gamma), as well as IL-1 alpha and turner necrosis factor-alpha, in both a time- and dose-dependent manner. IFN gamma-activation of the Janus (JAK) tyrosine kinases, JAK1 and JAK2 proteins, indicate that IFN gamma R, expressed in the Sertoli cell, is functional. Moreover, IFN gamma modulates the expression of interferon regulatory factor (IRF)-1 and IL-1 beta converting enzyme genes in Sertoli cells. Thus, our data are suggestive of a role(s) for IFN-gamma in the regulation of distinct gene expression and cell-specific sensitivity to apoptosis in the testis.