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Kwon, Hyug Moo
Immunometabolism and Cancer Lab.
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dc.citation.number 5 -
dc.citation.startPage eI167835 -
dc.citation.title JOURNAL OF CLINICAL INVESTIGATION -
dc.citation.volume 134 -
dc.contributor.author Li, Meiling -
dc.contributor.author Kim, Yu-Mi -
dc.contributor.author Koh, Jung Hee -
dc.contributor.author Park, Jihyun -
dc.contributor.author Kwon, Hyug Moo -
dc.contributor.author Park, Jong-Hwan -
dc.contributor.author Jin, Jingchun -
dc.contributor.author Park, Youngjae -
dc.contributor.author Kim, Donghyun -
dc.contributor.author Kim, Wan-Uk -
dc.date.accessioned 2024-05-03T10:35:26Z -
dc.date.available 2024-05-03T10:35:26Z -
dc.date.created 2024-04-30 -
dc.date.issued 2024-03 -
dc.description.abstract Nuclear factor of activated T -cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage -associated molecular pattern- triggered (DAMP -triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL -6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid -specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation. -
dc.identifier.bibliographicCitation JOURNAL OF CLINICAL INVESTIGATION, v.134, no.5, pp.eI167835 -
dc.identifier.doi 10.1172/JCI167835 -
dc.identifier.issn 0021-9738 -
dc.identifier.scopusid 2-s2.0-85186342168 -
dc.identifier.uri https://scholarworks.unist.ac.kr/handle/201301/82293 -
dc.identifier.wosid 001181739800011 -
dc.language 영어 -
dc.publisher AMER SOC CLINICAL INVESTIGATION INC -
dc.title Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5 -
dc.type Article -
dc.description.isOpenAccess TRUE -
dc.relation.journalWebOfScienceCategory Medicine, Research & Experimental -
dc.relation.journalResearchArea Research & Experimental Medicine -
dc.type.docType Article -
dc.description.journalRegisteredClass scie -
dc.description.journalRegisteredClass scopus -
dc.subject.keywordPlus ACUTE-PHASE REACTANTS -
dc.subject.keywordPlus RHEUMATOID-ARTHRITIS -
dc.subject.keywordPlus AMERICAN-COLLEGE -
dc.subject.keywordPlus PROTEIN -
dc.subject.keywordPlus MIGRATION -
dc.subject.keywordPlus RECEPTOR -
dc.subject.keywordPlus TRANSCRIPTION -
dc.subject.keywordPlus INFLAMMATION -
dc.subject.keywordPlus BINDING -
dc.subject.keywordPlus MECHANISMS -

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