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Identification and Regulation of Testicular Interferon- (IFN) Receptor Subunits: IFN Enhances Interferon Regulatory Factor-1 and Interleukin-1ß Converting Enzyme Expression¹

Population Council (M.K., P.L.M.) and The Rockefeller University (P.L.M.), New York, New York 10021

Address all correspondence and requests for reprints to: Dr. Patricia L. Morris, Center for Biomedical Research, Population Council and The Rockefeller University, 1230 York Avenue, New York, New York 10021. E-mail: p-morris{at}popcbr.rockefeller.edu

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

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