Document Detail


Distinct regulation of CD40-mediated interleukin-6 and interleukin-12 productions via mitogen-activated protein kinase and nuclear factor kappaB-inducing kinase in mature dendritic cells.
MedLine Citation:
PMID:  16556267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) pathways, especially NF-kappaB-inducing kinase (NIK)-mediated alternative pathway, in CD40-mediated interleukin (IL)-6 and IL-12 productions by immature or mature dendritic cells (DCs) was investigated. Murine myeloid DCs were matured by treatment with lipopolysaccharide. CD40 ligation induced modest or vigorous cytokine productions in immature or mature DCs, respectively. After CD40 ligation, p38 MAPK was significantly activated in either immature or mature DCs. SB203580, a p38 MAPK inhibitor, markedly decreased CD40-mediated IL-6 and IL-12 productions in immature DCs. In mature DCs, SB203580 significantly decreased CD40-mediated IL-6 but not IL-12 production. On the other hand, CD40 ligation induced vigorous activation of the NF-kappaB alternative pathway including p100 phosphorylation and subsequent nuclear translocations of p52, a processed form of p100, and RelB in mature but not immature DCs. The CD40-mediated phosphorylation of p100 was completely abolished in NIK-mutated mature DCs. The NIK mutation markedly reduced CD40-mediated IL-12 but not IL-6 production by mature DCs. Taken together, we concluded that IL-6 and IL-12 productions in response to CD40 ligation were controlled by p38 MAPK and NIK mediated alternative pathway, respectively, in mature DCs.
Authors:
Yoshiki Yanagawa; Kazunori Onoé
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  117     ISSN:  0019-2805     ISO Abbreviation:  Immunology     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-24     Completed Date:  2006-05-03     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  526-35     Citation Subset:  IM    
Affiliation:
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD40 / immunology*
Cell Differentiation / immunology
Cells, Cultured
Dendritic Cells / immunology*
Female
Interleukin-12 / biosynthesis
Interleukin-6 / biosynthesis
Interleukins / biosynthesis*
Mice
Mice, Inbred C57BL
NF-kappa B / metabolism
Phosphorylation
Protein-Serine-Threonine Kinases / immunology*
Signal Transduction / immunology
p38 Mitogen-Activated Protein Kinases / immunology*
Chemical
Reg. No./Substance:
0/Antigens, CD40; 0/Interleukin-6; 0/Interleukins; 0/NF-kappa B; 187348-17-0/Interleukin-12; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.11.25/NF-kappa B kinase
Comments/Corrections

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