Toll-like receptor 4 signaling is required for clusterin-induced tumor necrosis factor-alpha secretion in macrophage
DC Field | Value | Language |
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dc.contributor.author | Shim, Young Jun | - |
dc.contributor.author | Tae, Yoo-Keung | - |
dc.contributor.author | Kang, Byeong-Ho | - |
dc.contributor.author | Park, Jin-Sung | - |
dc.contributor.author | Jeon, Sol-Yi | - |
dc.contributor.author | Min, Bon-Hong | - |
dc.date.accessioned | 2021-09-03T10:48:00Z | - |
dc.date.available | 2021-09-03T10:48:00Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2017-01-22 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/84884 | - |
dc.description.abstract | Clusterin is a secretory glycoprotein that is up-regulated in areas of inflammation and under increased levels of oxidative stress. Previously, we demonstrated that clusterin activates NF-kappa B, and up-regulates the expression of MMP-9 and TNF-alpha. In this research, we extend our previous findings by reporting that such clusterin-induced macrophage response is mediated via TLR4 signaling. Specifically, we found that TNF-alpha induced by clusterin was significantly abrogated by pretreatment of TLR4-signaling inhibitors and anti-TLR4 neutralizing antibody. Additionally, a primary culture of macrophages derived from TLR4-signal defective and knockout mice were unresponsive to clusterin, resulting in no TNF-alpha secretion, whereas macrophages carrying wild-type TLR4 responded to clusterin and induced TNF-alpha. Moreover, clusterin increased NF-kappa B promoter activity in HER-Blue hTLR4 cells, but not in HER-Blue Null2 cells. To confirm that clusterin elicits TLR4 signal transduction, recombinant clusterin was generated and purified from cell culture. Interestingly, we found that the recombinant clusterin with C-terminal HA-tag induces TNF-alpha secretion at a significantly lower level compared to an intact form of clusterin without C-terminal HA-tag. Removal of HA-tag from the recombinant clusterin restored its activity, suggesting that C-terminal HA-tag partially masks the domain involved in TLR4 signaling. Furthermore, clusterin enhanced TLR4 mobilization into lipid raft of plasma membrane, and TNF-alpha and MMP-9 secretion stimulated by clusterin was diminished by pretreatment with methyl-beta-cyclodextrin (M beta CD), which was used to disrupt lipid raft. In conclusion, clusterin-induced TNF-alpha and MMP-9 up-regulation is most likely mediated via TLR4 recruitment into lipid rafts, and these data describe a novel role of clusterin as an endogenous regulator for TLR4 signaling. (C) 2016 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.subject | APOLIPOPROTEIN-J/CLUSTERIN | - |
dc.subject | CHEMOTACTIC MIGRATION | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | EXPRESSION | - |
dc.subject | PROTEIN | - |
dc.subject | LIGAND | - |
dc.subject | ACTIVATION | - |
dc.subject | PATHWAYS | - |
dc.title | Toll-like receptor 4 signaling is required for clusterin-induced tumor necrosis factor-alpha secretion in macrophage | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Min, Bon-Hong | - |
dc.identifier.doi | 10.1016/j.bbrc.2016.12.049 | - |
dc.identifier.scopusid | 2-s2.0-85008222807 | - |
dc.identifier.wosid | 000393720000136 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.482, no.4, pp.1407 - 1412 | - |
dc.relation.isPartOf | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.title | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.volume | 482 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 1407 | - |
dc.citation.endPage | 1412 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.subject.keywordPlus | APOLIPOPROTEIN-J/CLUSTERIN | - |
dc.subject.keywordPlus | CHEMOTACTIC MIGRATION | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | LIGAND | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | PATHWAYS | - |
dc.subject.keywordAuthor | Clusterin | - |
dc.subject.keywordAuthor | TLR4 | - |
dc.subject.keywordAuthor | TNF-alpha | - |
dc.subject.keywordAuthor | NF-kappa B | - |
dc.subject.keywordAuthor | Lipid raft | - |
dc.subject.keywordAuthor | Macrophage | - |
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