Activation of interleulin-9 receptor and downstream STAT3/5 in primary T-lymphomas in vivo in susceptible B6 and resistant C3H mouse

Deregulation of cytokine receptor expression and downstream signal transduction cascade play important roles in lymphoma development. It is reported that lymphoma and leukemia occasionally express both IL-9 and IL-9 receptor (IL-9R) and proliferate in response to IL-9 in vitro. In the present study, we investigated expression and biochemical characteristics of IL-9Ralpha and activation of downstream Jak-Stat signal transduction in primary T lymphoma (TL) arising in TL-prone B6 mice and resistant C3H. The results indicated that IL-9Ralpha and IL-9Ralpha protein is markedly expressed in B6 TL-cells. Three isoforms of IL-9Ralpha proteins with different glycosylation level were found in TL. The less glycosylated IL-9Ralpha was inclined to be the more phosphorylated, being an inverse relationship between glycosylation and phosphrylation. Normal thymocytes expressed the largest isoform of IL-9Ralpha only slightly. Phosphorylation of downstream Stat3 and Stat5 was also detected, but Stat1 activation was not. Overall phosphorylation of IL-9Ralpha and activation of downstream Stat3 and Stat5 was more elevated in B6 than C3H-TL, suggesting a link between IL-9R activation and radiation susceptibility to TL induction. In parallel with Stat5 phosphorylation, expression of cyclin D1 increased in B6-TL cells, while expression of Socs3, a negative regulator of Stat5, increased in C3H. These findings indicate that IL-9Ralpha and downstream Jak-Stat signal transduction were more activated in B6 than C3H TL cells, and that target genes of downstream Stat5 differed between these two strains.13th International Congress of Radiation Researc