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Interleukin-6 and IL-6 receptor cell expression in testis of rats with autoimmune orchitis.

Links Interleukin-6 and IL-6 receptor cell expression in testis of rats with autoimmune orchitis. Rival C, Theas MS, Guazzone VA, Lustig L

J Reprod Immunol. 2006 Jun;70(1-2):43-58. Epub 2006 Feb 3. Links Interleukin-6 and IL-6 receptor cell expression in testis of rats with autoimmune orchitis. Rival C, Theas MS, Guazzone VA, Lustig L. Centro de Investigaciones en Reproduccion, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 10, C1121 ABG Buenos Aires, Argentina. ciruba@fmed.uba.ar Experimental autoimmune orchitis (EAO) is an organ-specific model of autoimmunity characterized by an interstitial lymphomononuclear cell infiltrate as well as sloughing and apoptosis of germ cells. EAO was induced in adult male Sprague-Dawley rats by active immunization with testicular homogenate and adjuvants. Rats injected with saline solution and adjuvants were used as control group. The aim of this work was to study the expression of interleukin-6 (IL-6) and its receptor (IL-6R) in the testis of rats with EAO and analyze whether IL-6 could be involved in germ cell apoptosis. By immunohistochemistry, we detected IL-6 expression in testicular macrophages and Leydig cells of control and EAO rats. Sertoli cells showed IL-6 immunoreactivity in most of the seminiferous tubules of control rats, while a few IL-6+ Sertoli cells were found in the testis of rats with EAO. IL-6R immunoreactivity was observed in macrophages, Leydig and germ cells. A significant increase was noted in the number of IL-6R+ germ cells in rats with EAO compared to control rats. The content of IL-6 (ELISA) in the conditioned media obtained from testicular macrophages of rats with orchitis was significantly higher than in the control group. By immunofluorescence performed on isolated testicular macrophages, IL-6 was shown to be expressed by monocytes recently arrived from circulation (ED1+ cells), while resident macrophages (ED2+ cells) were negative. In vitro experiments (trypan blue and MTS assays) showed that IL-6 (50 ng/ml) reduced germ cell viability. We demonstrated also using the TUNEL technique that IL-6 added to cultures of seminiferous tubule segments induced apoptosis of germ cells. Our results suggest that IL-6 and IL-6R may be involved in the pathogenesis of autoimmune orchitis by promoting testicular inflammation and germ cell apoptosis. PMID: 16458979 [PubMed - indexed for MEDLINE] Related Links Involvement of tumor necrosis factor-alpha in the pathogenesis of autoimmune orchitis in rats. [Biol Reprod. 2003] PMID: 12606341 Monocyte chemoattractant protein-1 (MCP-1/CCL2) in experimental autoimmune orchitis. [J Reprod Immunol. 2003] PMID: 14638441 Death receptor and mitochondrial pathways are involved in germ cell apoptosis in an experimental model of autoimmune orchitis. [Hum Reprod. 2006] PMID: 16585127 Involvement of CD44 in leukocyte recruitment to the rat testis in experimental autoimmune orchitis. [Reproduction. 2005] PMID: 15855623 Effect of testicular macrophage conditioned media from rats with autoimmune orchitis on Leydig cell function. [Am J Reprod Immunol. 2000] PMID: 10735603 See all Related Articles... Display Summary Brief Abstract AbstractPlus Citation MEDLINE XML UI List LinkOut ASN.1 Related Articles Cited Articles Cited in Books CancerChrom Links Domain Links 3D Domain Links GEO DataSet Links Gene Links Gene (GeneRIF) Links Genome Links Project Links GENSAT Links GEO Profile Links HomoloGene Links Nucleotide Links Nucleotide (RefSeq) Links OMIA Links OMIM (calculated) Links OMIM (cited) Links BioAssay Links Compound Links Compound via MeSH Substance Links Substance via MeSH PMC Links Cited in PMC PopSet Links Probe Links Protein Links Protein (RefSeq) Links SNP Links Structure Links Taxonomy via GenBank UniGene Links UniSTS Links Show 5 10 20 50 100 200 500 Sort by Pub Date First Author Last Author Journal Send to Text File Printer Clipboard E-mail Order .

Centro de Investigaciones en Reproduccion, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 10, C1121 ABG Buenos Aires, Argentina. ciruba@fmed.uba.ar


Experimental autoimmune orchitis (EAO) is an organ-specific model of autoimmunity characterized by an interstitial lymphomononuclear cell infiltrate as well as sloughing and apoptosis of germ cells. EAO was induced in adult male Sprague-Dawley rats by active immunization with testicular homogenate and adjuvants. Rats injected with saline solution and adjuvants were used as control group. The aim of this work was to study the expression of interleukin-6 (IL-6) and its receptor (IL-6R) in the testis of rats with EAO and analyze whether IL-6 could be involved in germ cell apoptosis. By immunohistochemistry, we detected IL-6 expression in testicular macrophages and Leydig cells of control and EAO rats. Sertoli cells showed IL-6 immunoreactivity in most of the seminiferous tubules of control rats, while a few IL-6+ Sertoli cells were found in the testis of rats with EAO. IL-6R immunoreactivity was observed in macrophages, Leydig and germ cells. A significant increase was noted in the number of IL-6R+ germ cells in rats with EAO compared to control rats. The content of IL-6 (ELISA) in the conditioned media obtained from testicular macrophages of rats with orchitis was significantly higher than in the control group. By immunofluorescence performed on isolated testicular macrophages, IL-6 was shown to be expressed by monocytes recently arrived from circulation (ED1+ cells), while resident macrophages (ED2+ cells) were negative. In vitro experiments (trypan blue and MTS assays) showed that IL-6 (50 ng/ml) reduced germ cell viability. We demonstrated also using the TUNEL technique that IL-6 added to cultures of seminiferous tubule segments induced apoptosis of germ cells. Our results suggest that IL-6 and IL-6R may be involved in the pathogenesis of autoimmune orchitis by promoting testicular inflammation and germ cell apoptosis.




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