Strain difference in the activation of IL-9 receptor and JAK-STAT cascade in radiation-induced mice thymic lymphoma

Abstract

Dysregulation of cytokine receptor expression and downstream signal cascade plays important roles in lymphomagenesis. In this study, we compared activation of IL-9R-JAK-STAT cascade in radiation-induced thymic lymphoma (TL) between susceptible C57BL/6(B6) and resistant C3H mice. TL was induced by exposure to split-dose X-irradiation. Activation status of the pathway was investigated by western blotting and immunoprecipitation. The results obtained were as follows: (1) TL from B6 mice showed dramatically high expression of IL-9R protein as well as mRNA compared to normal thymocytes, and IL-9R was highly phosphorylated but less glycosylated, (2) high activation of JAK1, STAT3 and STAT5 were manifested in TL expressing high amount of IL-9R, and (3) in contrast to TL from B6, TL from C3H showed lower expression of IL-9R, and activation of JAK-STAT was also much infrequent. These findings suggest an association between the activation of JAK-STAT pathway possibly resulting from IL-9R over-expression and the TL-susceptibility in mice. Investigation of IL-9R transcription mechanism is in progress.