Interleukin-9 (IL-9) induces cell growth arrest associated with sustained signal transducer and activator of transcription activation in lymphoma cells overexpressing the IL-9 receptor

Murine interleukin (IL)-9 inhibits apoptosis in murine T lymphomas via sign al transducer and activator of transcription (STAT) factors. After transfec tion of the human IL-9 receptor, human IL-9 had a similar antiapoptotic act ivity, but, unlike the mouse protein, inhibited proliferation. This effect was correlated with the level of receptor expression and the extent of STAT phosphorylation. Expression of a moderate level of suppressor of cytokine signaling 3 (SOCS3) reduced STAT activation by human IL-9 and prevented inh ibition of growth but not of apoptosis. Using mutated IL-9 receptors, we sh owed that inhibition of proliferation was correlated with STAT1 and STAT3 a ctivation by IL-9 and induction of the cell cycle inhibitor p19/ink4d, a ST AT3 target gene. Activation of STAT1 by IFN-gamma did not result in cell gr owth arrest. In this model, cell growth inhibition is therefore associated with a higher number of receptors, a more robust STAT activation, and a gre ater sensitivity to SOCS3 expression, compared to apoptosis inhibition.