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

Abstract

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