IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1β and IL-6 production through a caspase 1-dependent mechanism

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dc.contributor.authorM G Netea-
dc.contributor.authorT Azam-
dc.contributor.authorG Ferwerda-
dc.contributor.authorS E Girardin-
dc.contributor.authorM Walsh-
dc.contributor.authorJ S Park-
dc.contributor.authorE Abraham-
dc.contributor.authorJ M Kim-
dc.contributor.authorDo Young Yoon-
dc.contributor.authorC A Dinarello-
dc.contributor.authorS H Kim-
dc.date.accessioned2017-04-19T09:03:33Z-
dc.date.available2017-04-19T09:03:33Z-
dc.date.issued2005-
dc.identifier.issn0027-8424-
dc.identifier.uri10.1073/pnas.0508237102ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/7137-
dc.description.abstractThe activation of innate immunity requires the amplification of signals induced by pattern-recognition receptors for bacterial products. We have investigated the role of the newly described cytokine IL-32 in the amplification of cytokine production induced by the two most clinically relevant families of microbial receptors, the cell-surface Toll-like receptors (TLRs) and the intracellular nuclear oligomerization domain (NOD) receptor family. IL-32 synergized with the NOD1- and NOD2-specific muropeptides of peptidoglycans for the release of IL-1β and IL-6 (a 3- to 10-fold increase). In contrast, IL-32 did not influence the cytokine production induced via TLRs. The synergistic effect of IL-32 and synthetic muramyl dipeptide (MDP) on cytokine production was absent in the cells of patients with Crohn's disease bearing the NOD2 frameshift mutation 3020insC, demonstrating that the IL-32/MDP synergism depends on NOD2. This in vitro synergism between IL-32 and NOD2 ligands was consistent with a marked constitutive expression of IL-32 in human colon epithelial tissue. In addition, the potentiating effect of IL-32 on the cytokine production induced by the synthetic muropeptide FK-156 was absent in NOD1-deficient macrophages, supporting the interaction between IL-32 and NOD1 pathways. When specific caspase inhibitors were used, the synergism between IL-32 and MDP/NOD2 depended on the activation of caspase 1. Only additive effects of IL-32 and muropeptides were observed for TNF-α production. The modulation of intracellular NOD2 pathways by IL-32, but not cell-surface TLRs, and the marked expression of IL-32 in colon mucosa suggest a role of IL-32 in the pathogenesis of Crohn's disease.-
dc.publisherNatl Acad Sciences-
dc.titleIL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1β and IL-6 production through a caspase 1-dependent mechanism-
dc.title.alternativeIL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1β and IL-6 production through a caspase 1-dependent mechanism-
dc.typeArticle-
dc.citation.titleProceedings of National Academy of Sciences of United States of America-
dc.citation.number45-
dc.citation.endPage16314-
dc.citation.startPage16309-
dc.citation.volume102-
dc.contributor.affiliatedAuthorDo Young Yoon-
dc.contributor.alternativeNameNetea-
dc.contributor.alternativeNameAzam-
dc.contributor.alternativeNameFerwerda-
dc.contributor.alternativeNameGirardin-
dc.contributor.alternativeNameWalsh-
dc.contributor.alternativeName박종성-
dc.contributor.alternativeNameAbraham-
dc.contributor.alternativeName김진만-
dc.contributor.alternativeName윤도영-
dc.contributor.alternativeNameDinarello-
dc.contributor.alternativeName김수현-
dc.identifier.bibliographicCitationProceedings of National Academy of Sciences of United States of America, vol. 102, no. 45, pp. 16309-16314-
dc.identifier.doi10.1073/pnas.0508237102-
dc.subject.keywordCytokines-
dc.subject.keywordToll-like receptors-
dc.subject.localcytokine-
dc.subject.localCytokines-
dc.subject.localCytokine-
dc.subject.localtoll-like receptors-
dc.subject.localToll-like receptor (TLR)-
dc.subject.localToll-like receptors-
dc.subject.localtoll-like receptor-
dc.subject.localTLR-
dc.subject.localtoll-like receptor (TLR)-
dc.subject.localToll-like receptor-
dc.description.journalClassY-
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