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

Abstract

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 alpha (TNFalpha) and interleukin 1beta (IL-1beta), 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-1beta also caused JNK phosphorylation and neutrophil recruitment to the testis. These results suggest that testicular IR injury stimulates IL-1beta 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.

Activation of Akt/Protein Kinase B and Extracellular Signal-regulated Kinase in Rats with Acute Experimental Testicular Torsion

“…However, we observed prolonged ERK1/2 activation during the first 6-24 hr of reperfusion. Recently, Lysiak et al [17] and Turner et al [32] reported a differential time-course in the activation of another mitogen-activated protein kinase (MAPK), SAPK/JNK, in acute testicular torsion, which is similar to the pattern of ERK activation observed here. Therefore, MAPK activation appears to play a role in the pathophysiology of testicular I/R injury.…”

Lycopene, an Antioxidant Carotenoid, Attenuates Testicular Injury Caused by Ischemia/Reperfusion in Rats

“…The minimal number of the samples was selected according to the basis of the previous studies (Lysiak et al 2003). Sham group received sham operation + 0.5 ml vehicle (corn oil) by gavage 5 min after the operation.…”

Palliative Effect of Pausinystallia macroceras on Testicular Ischemic Reperfusion Injury in Wistar Rats: a Histological Study

“…The pathophysiology involves stimulating an intracellular signaling cascade in the endothelial cells of the ischeamic vessels. This results in neutrophil recruitment, an increase in intracellular reactive oxygen species (ROS), and eventual germ cell specific apoptosis (Turner & Miller, 1997;Lysiak et al, 2001Lysiak et al, , 2003.…”