IDENTIFICATION AND REGULATION OF TESTICULAR INTERFERON-GAMMA (IFN-GAMMA) RECEPTOR SUBUNITS - IFN-GAMMA ENHANCES INTERFERON REGULATORY FACTOR-I AND INTERLEUKIN-1-BETA CONVERTING-ENZYME EXPRESSION

Interferon-gamma (IFN gamma) transmits its signal through a specific c ell surface receptor (IFN gamma), which consists of a primary ligand b inding alpha-chain (IFN gamma R alpha) and a signaling beta-chain (IFN gamma R beta). Recent studies identified the cytokines IFN gamma, int erleukin-6 (IL-6), IL-1 alpha, and tumor necrosis factor-or in testicu lar cells. Therefore, we: 1) examined the expression of IFN gamma R al pha 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) i dentified the cell signaling pathway components of testicular IFN gamm a R; and 4) characterized the functional role of testicular IFN gamma using primary Sertoli cells. We demonstrated the messenger RNAs for bo th chains of IFN gamma R in rat testicular cells using Northern hybrid ization analysis. Western blot analysis and immunocytochemistry showed that both specific IFN gamma R protein subunits were present in cultu red primary Leydig and Sertoli cells prepared from the testes of immat ure rats. The expression of both IFN gamma R component messenger RNAs in cultured Sertoli cells was increased by its specific ligand (IFN ga mma), 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 I L-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 ge ne expression and cell-specific sensitivity to apoptosis in the testis .