c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4

作者全名："Wu, Yi-Lin; Pan, Le-Han; Yi, Zhu-Jun; Zhang, Wen-Feng; Gong, Jian-Ping"

作者地址："[Wu, Yi-Lin; Pan, Le-Han; Yi, Zhu-Jun; Zhang, Wen-Feng; Gong, Jian-Ping] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China; [Yi, Zhu-Jun] Chongqing Univ Three Gorges Hosp, Dept Hepatobiliary Surg, Chongqing, Peoples R China"

通信作者："Zhang, WF; Gong, JP (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China."

来源：JOURNAL OF IMMUNOLOGY RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000967591100001

JCR分区：Q2

影响因子：3.5

年份：2023

卷号：2023

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："As a protective mechanism regulating excessive inflammation, endotoxin tolerance plays a vital role in regulating endotoxin shock. Kupffer cells are players in mediating endotoxin tolerance. Nonetheless, the regulatory mechanism regulating endotoxin tolerance is barely known. A nonclassical IKK kinase called TRAF-associated NF-kappa B activator (TANK)-binding kinase 1 (TBK1) can regulate inflammation. Here, we found that TBK1 is required for endotoxin tolerance in Kupffer cells. TBK1 plays a dominant role in regulating endotoxin tolerance by negatively regulating the induction of p100 processing. Deltex E3 ubiquitin ligase 4 (DTX4), a negative regulator of TBK1, can promote TBK1 K48-mediated ubiquitination and indirectly regulate endotoxin tolerance in Kupffer cells. We demonstrate that the c-Myb transcription factor could negatively regulate DTX4. Overexpression of c-Myb can be used to reduce the ubiquitination of TBK1 by reducing DTX4 transcription and to boost the anti-inflammatory effect of endotoxin tolerance. Thus, this study reveals a novel theory of TBK1-mediated endotoxin tolerance in Kupffer cells."

基金机构："National Natural Science Foundation of China [8197081191, 8180196]; China Postdoctoral Science Foundation [2019M653352, 2022MD723748]; Basic Key Program of Chongqing University Three Gorges Hospital [2022YJKYXM-002]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (grant nos. 8197081191 and 8180196), the China Postdoctoral Science Foundation (grant nos. 2019M653352 and 2022MD723748), and Basic Key Program of Chongqing University Three Gorges Hospital (grant no. 2022YJKYXM-002)."