Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex
DC Field | Value | Language |
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dc.contributor.author | Kim, So Yeon | - |
dc.contributor.author | Jeong, Jong-Min | - |
dc.contributor.author | Kim, Soo Jin | - |
dc.contributor.author | Seo, Wonhyo | - |
dc.contributor.author | Kim, Myung-Ho | - |
dc.contributor.author | Choi, Won-Mook | - |
dc.contributor.author | Yoo, Wonbeak | - |
dc.contributor.author | Lee, Jun-Hee | - |
dc.contributor.author | Shim, Young-Ri | - |
dc.contributor.author | Yi, Hyon-Seung | - |
dc.contributor.author | Lee, Young-Sun | - |
dc.contributor.author | Eun, Hyuk Soo | - |
dc.contributor.author | Lee, Byung Seok | - |
dc.contributor.author | Chun, Kwangsik | - |
dc.contributor.author | Kang, Suk-Jo | - |
dc.contributor.author | Kim, Sun Chang | - |
dc.contributor.author | Gao, Bin | - |
dc.contributor.author | Kunos, George | - |
dc.contributor.author | Kim, Ho Min | - |
dc.contributor.author | Jeong, Won-Il | - |
dc.date.accessioned | 2021-09-02T21:49:56Z | - |
dc.date.available | 2021-09-02T21:49:56Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2017-12-21 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/81142 | - |
dc.description.abstract | Reactive oxygen species (ROS) contribute to the development of non-alcoholic fatty liver disease. ROS generation by infiltrating macrophages involves multiple mechanisms, including Toll-like receptor 4 (TLR4)-mediated NADPH oxidase (NOX) activation. Here, we show that palmitate-stimulated CD11b(+)F4/80(low) hepatic infiltrating macrophages, but not CD11b(+)F4/80(high) Kupffer cells, generate ROS via dynamin-mediated endocytosis of TLR4 and NOX2, independently from MyD88 and TRIF. We demonstrate that differently from LPS-mediated dimerization of the TLR4-MD2 complex, palmitate binds a monomeric TLR4-MD2 complex that triggers endocytosis, ROS generation and increases pro-interleukin-1 beta expression in macrophages. Palmitate-induced ROS generation in human CD68(low)CD14(high) macrophages is strongly suppressed by inhibition of dynamin. Furthermore, Nox2-deficient mice are protected against high-fat diet-induced hepatic steatosis and insulin resistance. Therefore, endocytosis of TLR4 and NOX2 into macrophages might be a novel therapeutic target for non-alcoholic fatty liver disease. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | REACTIVE OXYGEN | - |
dc.subject | NLRP3 INFLAMMASOME | - |
dc.subject | ISOLATION STRESS | - |
dc.subject | ADIPOSE-TISSUE | - |
dc.subject | FATTY-ACIDS | - |
dc.subject | NOX FAMILY | - |
dc.subject | RECEPTOR 4 | - |
dc.subject | ACTIVATION | - |
dc.subject | LIVER | - |
dc.subject | EXPRESSION | - |
dc.title | Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Young-Sun | - |
dc.identifier.doi | 10.1038/s41467-017-02325-2 | - |
dc.identifier.scopusid | 2-s2.0-85042357204 | - |
dc.identifier.wosid | 000418567200014 | - |
dc.identifier.bibliographicCitation | NATURE COMMUNICATIONS, v.8 | - |
dc.relation.isPartOf | NATURE COMMUNICATIONS | - |
dc.citation.title | NATURE COMMUNICATIONS | - |
dc.citation.volume | 8 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | REACTIVE OXYGEN | - |
dc.subject.keywordPlus | NLRP3 INFLAMMASOME | - |
dc.subject.keywordPlus | ISOLATION STRESS | - |
dc.subject.keywordPlus | ADIPOSE-TISSUE | - |
dc.subject.keywordPlus | FATTY-ACIDS | - |
dc.subject.keywordPlus | NOX FAMILY | - |
dc.subject.keywordPlus | RECEPTOR 4 | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | EXPRESSION | - |
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