Author:
Cheng Yinglan,Manabe Ichiro,Hayakawa Sumio,Endo Yusuke,Oishi Yumiko
Abstract
Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that control fatty acid and cholesterol metabolism. As the major SREBP isoform in macrophages, SREBP1a is also required for inflammatory and phagocytotic functions. However, it is insufficiently understood how SREBP1a is activated by the innate immune response in macrophages. Here, we show that mouse caspase-11 is a novel inflammatory activator of SREBP1a in macrophages. Upon LPS treatment, caspase-11 was found to promote the processing of site-1 protease (S1P), an enzyme that mediates the cleavage and activation of SREBP1. We also determined that caspase-11 directly associates with S1P and cleaves it at a specific site. Furthermore, deletion of the Casp4 gene, which encodes caspase-11, impaired the activation of S1P and SREBP1 as well as altered the expression of genes regulated by SREBP1 in macrophages. These results demonstrate that the caspase-11/S1P pathway activates SREBP1 in response to LPS, thus regulating subsequent macrophage activation.
Funder
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Japan Science and Technology Agency
Takeda Medical Research Foundation
Mitsubishi Foundation
Subject
Immunology,Immunology and Allergy
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献