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.
Richard
M
M
Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.
Louahed
J
J
Demoulin
J B
JB
Renauld
J C
JC
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000494:pharmacology; D019281:Dimerization; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008894:Milk Proteins; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D004268:DNA-Binding Proteins; D016906:Interleukin-9; D008894:Milk Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4