IL-9 induces 24P3 lipocalin gene expression in murine T cell lymphomas

Orabona, Ciriana [UCL] Dumoutier, Laure [UCL] Renauld, Jean-Christophe [UCL]

Interleukin-9 (IL-9) is a Th2 cytokine whose overexpression is associated with asthma and T cell lymphomagenesis, All the IL-9 activities studied so far are mediated by a specific hemopoietin receptor that activates a Jak/STAT pathway. Searching for genes specifically modulated by IL-9, we observed that the 24P3 mRNA is strongly upregulated in BW5147 T lymphoma cells upon IL-9 stimulation, 24P3 is a member of the lipocalin family, and has been reported to bind N-formyl-Met-Leu-Phe, a potent neutrophil chemoattractant, and possibly other lipophylic mediators of inflammation. A similar 24P3 induction was observed in other T cell lymphomas (EL4 and TH201) in response to IL-9, as well as in EL4 cells stimulated with IL-6 or IL-1, By contrast, other IL-9-responsive cells such as mast cell line MC9 and B cell lymphoma A20 showed no 24P3 induction upon IL-9 stimulation. Experiments using IL-9R mutants indicated that STAT transcription factors, particularly STAT3, are involved in this process. However, 24P3 gene induction was slow, reaching a plateau from 36 to 72 hours after stimulation and was inhibited if cells were treated with cycloheximide during the first 8 hours of IL-9 stimulation, suggesting an indirect induction requiring new protein synthesis.