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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2011-6-7
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6848-59
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
IL-32gamma induces the maturation of dendritic cells with Th1- and Th17-polarizing ability through enhanced IL-12 and IL-6 production.
pubmed:affiliation
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't