Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex
- Authors
- Kim, So Yeon; Jeong, Jong-Min; Kim, Soo Jin; Seo, Wonhyo; Kim, Myung-Ho; Choi, Won-Mook; Yoo, Wonbeak; Lee, Jun-Hee; Shim, Young-Ri; Yi, Hyon-Seung; Lee, Young-Sun; Eun, Hyuk Soo; Lee, Byung Seok; Chun, Kwangsik; Kang, Suk-Jo; Kim, Sun Chang; Gao, Bin; Kunos, George; Kim, Ho Min; Jeong, Won-Il
- Issue Date
- 21-12월-2017
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.8
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 8
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/81142
- DOI
- 10.1038/s41467-017-02325-2
- ISSN
- 2041-1723
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.