Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction.

BCL3 encodes a protein with close homology to IkappaB proteins and interacts with p50 NF-kappaB homodimers. However, the regulation and transcriptional activity of BCL3 remain ill-defined. We observed here that interleukin-9 (IL-9) and IL-4, but not IL-2 or IL-3, transcriptionally upregulated BCL3 expression in T cells and mast cells. BCL3 induction by IL-9 was detected as soon as 4 hours after stimulation and appeared to be dependent on the Jak/STAT pathway. IL-9 stimulation was associated with an increase in p50 homodimers DNA binding activity, which was mimicked by stable BCL3 expression. This contrasts with tumor necrosis factor (TNF)-dependent NF-kappaB activation, which occurs earlier, involves p65/p50 dimers, and is dependent on IkappaB degradation. Moreover, IL-9 stimulation or BCL3 transient transfection similarly inhibited NF-kappaB-mediated transcription in response to TNF. Taken together, our observations show a new regulatory pathway for the NF-kappaB transcription factors through STAT-dependent upregulation of BCL3 gene expression.