Interleukin-9 regulates NF-κB activity through BCL3 gene induction

BCL3 encodes a protein with close homology to I kappa B proteins and interacts with p50 NF-kappa B 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-kappa B activation, which occurs earlier, involves p65/p50 dimers, and is dependent on I kappa B degradation. Moreover, IL-9 stimulation or BCL3 transient transfection similarly inhibited NF-kappa B-mediated transcription in response to TNF, Taken together, our observations show a new regulatory pathway for the NF-kappa B transcription factors through STAT-dependent upregulation of BCL3 gene expression. (C) 1999 by The American Society of Hematology.