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Am J Physiol Regul Integr Comp Physiol (January 20, 2005). doi:10.1152/ajpregu.00651.2004
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Submitted on September 22, 2004
Accepted on January 10, 2005

Cytokine Profiles in the Testes of Rats Treated with Lipopolysaccharide Reveal Localized Suppression of Inflammatory Responses

Moira K O'Bryan1, Orapin Gerdprasert2, David J Nikolic-Paterson3, Andreas Meinhardt4, Julie A Muir2, Lynda M Foulds2, David J Phillips2, David M de Kretser1, and Mark P Hedger2*

1 Monash Institute of Reproduction and Development, Monash University, Clayton, 3168, Australia; Australian Research Centre of Excellence in Biotechnology and Development, Monash University, Clayton, 3168, Australia
2 Monash Institute of Reproduction and Development, Monash University, Clayton, 3168, Australia
3 Department of Nephrology, Monash Medical Centre, Clayton, 3168, Australia
4 Institut fur Anatomie und Zellbiologie, Justus-Liebig-University of Giessen, Giessen, D-35385, Germany

* To whom correspondence should be addressed. E-mail: mark.hedger{at}med.monash.edu.au.

Evidence indicates that the testis possesses a reduced capacity to mount inflammatory and rejection responses, which undoubtedly contributes to the ongoing survival of the highly immunogenic germ cells. The contribution of local cytokine expression to this condition was investigated in adult male rats treated with lipopolysaccharide to induce inflammation. Cytokine mRNA and protein expression were determined in tissue extracts and fluids by Northern blot analysis, quantitative PCR or RNAse protection assay and specific ELISAs. Testicular expression of the pro-inflammatory cytokines, interleukin-1{beta} (IL-1{beta}) and tumor necrosis factor-{alpha} (TNF{alpha}) was considerably attenuated compared with the liver (control tissue); in contrast, the testicular IL-6 response was enhanced. Expression of IL-10, a type 2 immunoregulatory cytokine, was similar in both testis and liver, while the immunoregulatory/anti-inflammatory cytokines, transforming growth factor-{beta}1 (TGF{beta}1) and activin A were constitutively elevated in both normal and inflamed testes. The IL-1{beta} and TGF{beta}1 proteins were present principally in their latent (inactive) forms, indicating that enzymic processing is an important control mechanism for these two cytokines within the testis. These data indicate that inflammatory and regulatory cytokine activity is regulated at both transcriptional and post-translational levels in a testis-specific manner. It is concluded that a novel pattern of suppression of pro-inflammatory cytokine responses and normal or elevated expression of immunoregulatory cytokines may be responsible for reduced inflammatory responses and enhanced graft survival in the testis. These data have important implications for the understanding and treatment of male autoimmune infertility, testicular inflammation and carcinogenesis.




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