Bibliographic Details
| Title: |
Caspase-11 contributes to site-1 protease cleavage and SREBP1 activation in the inflammatory response of macrophages |
| Authors: |
Yinglan Cheng, Ichiro Manabe, Sumio Hayakawa, Yusuke Endo, Yumiko Oishi |
| Source: |
Frontiers in Immunology, Vol 14 (2023) |
| Publisher Information: |
Frontiers Media S.A., 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
macrophage, SREBP (sterol regulatory element-binding protein) pathway, site-1 protease (S1P), caspase, inflammatory response, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1009973/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2023.1009973 |
| Access URL: |
https://doaj.org/article/5647a29f740c45039fbe8e5e0c22d9e6 |
| Accession Number: |
edsdoj.5647a29f740c45039fbe8e5e0c22d9e6 |
| Database: |
Directory of Open Access Journals |
