CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: involvement of NF-kappa B, AP-1, and C/EBP

Mekhine Baccam; So-Youn Woo; Charles Vinson; Gail A Bishop

doi:10.4049/jimmunol.170.6.3099

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CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: involvement of NF-kappa B, AP-1, and C/EBP

Journal article

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Peer reviewed

CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: involvement of NF-kappa B, AP-1, and C/EBP

Mekhine Baccam, So-Youn Woo, Charles Vinson and Gail A Bishop

The Journal of immunology (1950), Vol.170(6), pp.3099-3108

03/15/2003

DOI: 10.4049/jimmunol.170.6.3099

PMID: 12626566

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Abstract

Engagement of CD40 by its ligand CD154 induces IL-6 production by B lymphocytes. We previously reported that this IL-6 production is dependent upon binding of the adapter protein TNF receptor-associated factor 6 to the cytoplasmic domain of CD40, while binding of TNF receptor-associated factors 2 and 3 is dispensable, as is the activation-induced nuclear translocation of NF-kappa B. The present study was designed to characterize CD40-mediated transcriptional control of the IL-6 gene in B cells. CD40 engagement on B lymphocytes activated the IL-6 promoter, and mutations in the putative binding sites for AP-1 and C/EBP transcription factors reduced this activation. Interestingly, a mutation in the putative NF-kappa B binding site completely abrogated the basal promoter activity, thus also rendering the promoter unresponsive to CD40 stimulation, suggesting that this site is required for binding of NF-kappa B constitutively present in the nucleus of mature B cells. The expression of dominant negative Fos or C/EBP alpha proteins, which prevent binding of AP-1 or C/EBP complexes to DNA, also reduced CD40-mediated IL-6 gene expression. Furthermore, CD40 stimulation led to phosphorylation of c-Jun on its activation domain, implicating CD40-mediated Jun kinase activation in the transcriptional regulation of IL-6 production.

Protein Structure, Tertiary

CD40 Antigens - physiology

Cell Line

Phosphorylation

Interleukin-6 - genetics

Mice, Inbred C57BL

Transcriptional Activation - immunology

Serine - metabolism

Signal Transduction - immunology

Lymphocyte Activation - immunology

Animals

B-Lymphocytes - immunology

Proto-Oncogene Proteins c-jun - metabolism

CCAAT-Enhancer-Binding Proteins - physiology

Transcription Factor AP-1 - physiology

NF-kappa B - physiology

Transcription, Genetic - immunology

Mice

Promoter Regions, Genetic - immunology

Interleukin-6 - metabolism

B-Lymphocytes - metabolism

Immunoglobulin M - biosynthesis

Details

Title: Subtitle: CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: involvement of NF-kappa B, AP-1, and C/EBP
Creators: Mekhine Baccam - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
So-Youn Woo
Charles Vinson
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.170(6), pp.3099-3108
Publisher: United States
DOI: 10.4049/jimmunol.170.6.3099
PMID: 12626566
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: AI49993 / NIAID NIH HHS AI28847 / NIAID NIH HHS
Language: English
Date published: 03/15/2003
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001115502771

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