Cited 33 times in
Indoxyl sulfate-induced TNF-α is regulated by crosstalk between the aryl hydrocarbon receptor, NF-κB, and SOCS2 in human macrophages
DC Field | Value | Language |
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dc.contributor.author | 김현창 | - |
dc.contributor.author | 유태현 | - |
dc.date.accessioned | 2019-12-18T00:53:38Z | - |
dc.date.available | 2019-12-18T00:53:38Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/173263 | - |
dc.description.abstract | Indoxyl sulfate (IS) is a uremic toxin associated with increased prevalence of cardiovascular diseases (CVDs) in patients with chronic kidney disease. Despite the crucial role of uremia-related immune dysfunction, a majority of studies attempting to elucidate its pathogenic role in CVD have focused on IS-mediated endothelial dysfunction. Thus, we investigated the underlying molecular mechanisms involved in IS-induced production of TNF-α, a major cardiotoxic cytokine, by human macrophages. We found that crosstalk between the aryl hydrocarbon receptor (AhR), NF-κB, and the suppressor of cytokine signaling (SOCS)2 is important for TNF-α production in IS-stimulated human macrophages. IS-activated AhR rapidly associates with the p65 NF-κB subunit, resulting in mutual inhibition of AhR and NF-κB and inhibition of TNF-α production at an early time point. Later, this repression of TNF-α production is alleviated when SOCS2, a negative modulator of NF-κB, is directly induced by IS-activated AhR. In addition, once free of inhibition, activated AhR induces TNF-α expression by interacting with AhR binding sites in the TNF-α gene. Lastly, we confirmed decreased AhR and increased SOCS2 expression in monocytes of patients with end-stage renal disease, indicating the activation of AhR. Taken together, our results suggest that IS-induced TNF-α production in macrophages is regulated through a complicated mechanism involving interaction of AhR, NF-κB, and SOCS2.-Kim, H. Y., Yoo, T.-H., Cho, J.-Y., Kim, H. C., Lee, W.-W. Indoxyl sulfate-induced TNF-α is regulated by crosstalk between the aryl hydrocarbon receptor, NF-κB, and SOCS2 in human macrophages. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | The Federation | - |
dc.relation.isPartOf | FASEB JOURNAL | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Indoxyl sulfate-induced TNF-α is regulated by crosstalk between the aryl hydrocarbon receptor, NF-κB, and SOCS2 in human macrophages | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Preventive Medicine and Public Health (예방의학교실) | - |
dc.contributor.googleauthor | Hee Young Kim | - |
dc.contributor.googleauthor | Tae-Hyun Yoo | - |
dc.contributor.googleauthor | Joo-Youn Cho | - |
dc.contributor.googleauthor | Hyeon Chang Kim | - |
dc.contributor.googleauthor | Won-Woo Lee | - |
dc.identifier.doi | 10.1096/fj.201900730R | - |
dc.contributor.localId | A01142 | - |
dc.contributor.localId | A02526 | - |
dc.relation.journalcode | J00889 | - |
dc.identifier.eissn | 1530-6860 | - |
dc.identifier.pmid | 31284759 | - |
dc.identifier.url | https://www.fasebj.org/doi/full/10.1096/fj.201900730R | - |
dc.subject.keyword | AhR | - |
dc.subject.keyword | CVD | - |
dc.subject.keyword | ESRD | - |
dc.subject.keyword | HMDM | - |
dc.subject.keyword | IS | - |
dc.contributor.alternativeName | Kim, Hyeon Chang | - |
dc.contributor.affiliatedAuthor | 김현창 | - |
dc.contributor.affiliatedAuthor | 유태현 | - |
dc.citation.volume | 33 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 10844 | - |
dc.citation.endPage | 10858 | - |
dc.identifier.bibliographicCitation | FASEB JOURNAL, Vol.33(10) : 10844-10858, 2019 | - |
dc.identifier.rimsid | 63198 | - |
dc.type.rims | ART | - |
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