TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation

Tony J Vanden Bush; Gail A Bishop

doi:10.1002/eji.200737602

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TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation

Journal article

Open access

Peer reviewed

TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation

Tony J Vanden Bush and Gail A Bishop

European journal of immunology, Vol.38(2), pp.400-409

02/2008

DOI: 10.1002/eji.200737602

PMCID: PMC2951126

PMID: 18228247

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Abstract

During vaccination or infection, adaptive and innate immune receptors of B cells are engaged by microbial antigens/ligands. A better understanding of how innate and adaptive signaling pathways interact could enlighten B lymphocyte biology as well as aid immunotherapy strategies and vaccine design. To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation. Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals. The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos. Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity. The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos. The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity. In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells.

CD40 Antigens - physiology

Humans

Mice, Inbred C57BL

Cells, Cultured

JNK Mitogen-Activated Protein Kinases - metabolism

Transcription Factor AP-1 - metabolism

Signal Transduction - immunology

Lymphocyte Activation - immunology

Membrane Glycoproteins - physiology

Animals

B-Lymphocytes - immunology

Toll-Like Receptor 7 - physiology

Toll-Like Receptor 8 - physiology

Transcription Factor AP-1 - physiology

JNK Mitogen-Activated Protein Kinases - physiology

Cell Line, Tumor

Interleukin-6 - biosynthesis

Adult

Mice

Cytokines - biosynthesis

Details

Title: Subtitle: TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation
Creators: Tony J Vanden Bush - Department of Microbiology, The University of Iowa, Iowa City, IA 52242, USA
Gail A Bishop
Resource Type: Journal article
Publication Details: European journal of immunology, Vol.38(2), pp.400-409
DOI: 10.1002/eji.200737602
PMID: 18228247
PMCID: PMC2951126
NLM abbreviation: Eur J Immunol
ISSN: 0014-2980
eISSN: 1521-4141
Publisher: Germany
Grant note: R56 AI049993-10 / NIAID NIH HHS R01 AI028847 / NIAID NIH HHS R01 AI049993 / NIAID NIH HHS R56 AI049993 / NIAID NIH HHS R01 AI028847-09 / NIAID NIH HHS R01 AI049993-01 / NIAID NIH HHS R01 CA099997-01 / NCI NIH HHS AI 49993 / NIAID NIH HHS AI 28847 / NIAID NIH HHS R01 AI028847-20 / NIAID NIH HHS R01 CA099997-08 / NCI NIH HHS R01 CA099997 / NCI NIH HHS R56 AI028847 / NIAID NIH HHS CA 099997 / NCI NIH HHS
Language: English
Date published: 02/2008
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001141802771

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