Source:http://linkedlifedata.com/resource/pubmed/id/21551364
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2011-6-7
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pubmed:abstractText |
IL-32, a newly described multifunctional cytokine, has been associated with a variety of inflammatory diseases, including rheumatoid arthritis, vasculitis, and Crohn's disease. In this study, we investigated the immunomodulatory effects of IL-32? on bone marrow-derived dendritic cell (DC)-driven Th responses and analyzed the underlying signaling events. IL-32?-treated DCs exhibited upregulated expression of cell-surface molecules and proinflammatory cytokines associated with DC maturation and activation. In particular, IL-32? treatment significantly increased production of IL-12 and IL-6 in DCs, which are known as Th1- and Th17-polarizing cytokines, respectively. This increased production was inhibited by the addition of specific inhibitors of the activities of phospholipase C (PLC), JNK, and NF-?B. IL-32? treatment increased the phosphorylation of JNK and the degradation of both I?B? and I?B? in DCs, as well as NF-?B binding activity to the ?B site. The PLC inhibitor suppressed NF-?B DNA binding activity and JNK phosphorylation increased by IL-32? treatment, thereby indicating that IL-32? induced IL-12 and IL-6 production in DCs via a PLC/JNK/NF-?B signaling pathway. Importantly, IL-32?-stimulated DCs significantly induced both Th1 and Th17 responses when cocultured with CD4(+) T cells. The addition of a neutralizing anti-IL-12 mAb abolished the secretion of IFN-? in a dose-dependent manner; additionally, the blockage of IL-1? and IL-6, but not of IL-21 or IL-23p19, profoundly inhibited IL-32?-induced IL-17 production. These results demonstrated that IL-32? could effectively induce the maturation and activation of immature DCs, leading to enhanced Th1 and Th17 responses as the result of increased IL-12 and IL-6 production in DCs.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
186
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6848-59
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pubmed:meshHeading |
pubmed-meshheading:21551364-Animals,
pubmed-meshheading:21551364-CD4-Positive T-Lymphocytes,
pubmed-meshheading:21551364-Cell Differentiation,
pubmed-meshheading:21551364-Coculture Techniques,
pubmed-meshheading:21551364-Dendritic Cells,
pubmed-meshheading:21551364-Female,
pubmed-meshheading:21551364-Humans,
pubmed-meshheading:21551364-Interleukin-12,
pubmed-meshheading:21551364-Interleukin-6,
pubmed-meshheading:21551364-Interleukins,
pubmed-meshheading:21551364-Mice,
pubmed-meshheading:21551364-Signal Transduction,
pubmed-meshheading:21551364-Th1 Cells,
pubmed-meshheading:21551364-Th17 Cells,
pubmed-meshheading:21551364-Up-Regulation
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pubmed:year |
2011
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pubmed:articleTitle |
IL-32gamma induces the maturation of dendritic cells with Th1- and Th17-polarizing ability through enhanced IL-12 and IL-6 production.
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pubmed:affiliation |
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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