title: IL-4-stimulated NF-kappaB activity is required for Stat6 DNA binding.
abstract: IL-4 is a critical cytokine in the regulation of immune responses. In B lymphocytes, IL-4 signaling promotes the Stat6-dependent cell surface expression of several proteins including MHC Class II and CD86. However, the requirement for other transcription factors in IL-4-induced B cell gene expression has not been studied extensively. Here, we show that IL-4 induces NF-kappaB p100 processing to NF-kappaB p52 in B cells but not in T cells or macrophages. IL-4 induced NF-kappaB p52 production requires PI-3K activity and correlates with IkappaB kinase phosphorylation and TNF receptor-associated factor 3 degradation. Blocking NF-kappaB activity eliminates IL-4-stimulated gene expression in B cells by reducing IL-4-induced DNA binding but not phosphorylation or nuclear localization of Stat6. These results describe a novel role for NF-kappaB in IL-4-induced signaling and gene expression.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, and Walther Cancer Institute, Indianapolis, Indiana, USA.
authors.forename: Vivian T
authors.initials: VT
authors.lastname: Thieu
authors.forename: Evelyn T
authors.initials: ET
authors.lastname: Nguyen
authors.forename: Brian P
authors.initials: BP
authors.lastname: McCarthy
authors.forename: Heather A
authors.initials: HA
authors.lastname: Bruns
authors.forename: Reuben
authors.initials: R
authors.lastname: Kapur
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D017930:Genes, Reporter; D015847:Interleukin-4 / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D050800:STAT6 Transcription Factor / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D004247:DNA; D008156:Luciferases