HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 69/1/202    most recent biolreprod.102.013318v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lysiak, J. J. Articles by Turner, T. T. Search for Related Content PubMed PubMed Citation Articles by Lysiak, J. J. Articles by Turner, T. T. Agricola Articles by Lysiak, J. J. Articles by Turner, T. T.

Ischemia-Reperfusion of the Murine Testis Stimulates the Expression of Proinflammatory Cytokines and Activation of c-jun N-Terminal Kinase in a Pathway to E-Selectin Expression¹

Departments of Urology³ Cell Biology,⁴ University of Virginia Health Science System, Charlottesville, Virginia 22908

Ischemia-reperfusion (IR) of the testis results in germ cell-specific apoptosis and can lead to aspermatogenesis. Germ cell-specific apoptosis after IR of the testis has been shown to be correlated with and dependent on neutrophil recruitment to the testis after IR. Studies that used E-selectin-deficient mice have demonstrated that E-selectin expression is critical for neutrophil recruitment to subtunical venules in the testis after IR and for the resultant germ cell-specific apoptosis. The present study investigates the in vivo signaling pathway that exists after IR that leads to neutrophil recruitment in the murine testis. Mice were subjected to a 2-h period of testicular ischemia followed by reperfusion. Results demonstrate that the proinflammatory cytokines, tumor necrosis factor (TNF) and interleukin 1ß (IL-1ß), are stimulated after IR as is the phosphorylation of c-jun N-terminal kinase (JNK). The downstream transcription factors of JNK, ATF-2 and c-jun are also phosphorylated at specific times after IR of the testis. Activation of the JNK stress-related kinase pathway is correlated with an increase in E-selectin expression and neutrophil recruitment to the testis after IR. Intratesticular injection of IL-1ß also caused JNK phosphorylation and neutrophil recruitment to the testis. These results suggest that testicular IR injury stimulates IL-1ß expression, which leads to activation of the JNK signaling pathway and ultimately E-selectin expression and neutrophil recruitment to the testis. This provides the first evidence of a cytokine/stress-related kinase signaling pathway to E-selectin expression in vivo.

¹ Supported by the National Institutes of Health grant RO1-DK-53072 (to T.T.T.), the Medical Scientist Training Program National Institutes of Health grant 2T32 GM07267 (to J.L.K.), and a grant from the AFUD/AUA Research Scholar Program (to J.J.L.).

² Correspondence: Jeffrey J. Lysiak, Department of Urology, Box 800422, University of Virginia Health Science System, Charlottesville, VA 22908. FAX: 434 924 8311; jl6n{at}virginia.edu

This article has been cited by other articles:

				T. T. Turner and J. J. Lysiak Oxidative Stress: A Common Factor in Testicular Dysfunction J Androl, September 1, 2008; 29(5): 488 - 498. [Abstract] [Full Text] [PDF]

				M. D. Show, C. M. Hill, M. D. Anway, W. W. Wright, and B. R. Zirkin Phosphorylation of Mitogen-Activated Protein Kinase 8 (MAPK8) Is Associated With Germ Cell Apoptosis and Redistribution of the Bcl2-Modifying Factor (BMF) J Androl, May 1, 2008; 29(3): 338 - 344. [Abstract] [Full Text] [PDF]

				T. T. Turner, J. J. Lysiak, J. D. Shannon, Q. A. T. Nguyen, and C. R. Bazemore-Walker Testicular Torsion Alters the Presence of Specific Proteins in the Mouse Testis as Well as the Phosphorylation Status of Specific Proteins J Androl, March 1, 2006; 27(2): 285 - 293. [Abstract] [Full Text] [PDF]

				L. Minutoli, P. Antonuccio, C. Romeo, P. A. Nicotina, A. Bitto, S. Arena, F. Polito, D. Altavilla, N. Turiaco, A. Cutrupi, et al. Evidence for a Role of Mitogen-Activated Protein Kinase 3/Mitogen-Activated Protein Kinase in the Development of Testicular Ischemia-Reperfusion Injury Biol Reprod, October 1, 2005; 73(4): 730 - 736. [Abstract] [Full Text] [PDF]

				J. J. Lysiak, H. J. Bang, Q. A. T. Nguyen, and T. T. Turner Activation of the Nuclear Factor Kappa B Pathway Following Ischemia-Reperfusion of the Murine Testis J Androl, January 1, 2005; 26(1): 129 - 135. [Abstract] [Full Text] [PDF]