SERPINB1-mediated checkpoint of inflammatory caspase activation
- Authors
- Choi, Youn Jung; Kim, Stephanie; Choi, Younho; Nielsen, Travis B.; Yan, Jun; Lu, Alvin; Ruan, Jianbin; Lee, Hye-Ra; Wu, Hao; Spellberg, Brad; Jung, Jae U.
- Issue Date
- 3월-2019
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE IMMUNOLOGY, v.20, no.3, pp.276 - +
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE IMMUNOLOGY
- Volume
- 20
- Number
- 3
- Start Page
- 276
- End Page
- +
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/67220
- DOI
- 10.1038/s41590-018-0303-z
- ISSN
- 1529-2908
- Abstract
- Inflammatory caspases (caspase-1, caspase-4, caspase-5 and caspase-11 (caspase-1/-4/-5/-11)) mediate host defense against microbial infections, processing pro-inflammatory cytokines and triggering pyroptosis. However, precise checkpoints are required to prevent their unsolicited activation. Here we report that serpin family B member 1 (SERPINB1) limited the activity of those caspases by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation. While the reactive center loop of SERPINB1 inhibits neutrophil serine proteases, its carboxy-terminal CARD-binding motif restrained the activation of pro-caspase-1/-4/-5/-11. Consequently, knockdown or deletion of SERPINB1 prompted spontaneous activation of caspase-1/-4/-5/-11, release of the cytokine IL-1 beta and pyroptosis, inducing elevated inflammation after non-hygienic co-housing with pet-store mice and enhanced sensitivity to lipopolysaccharide- or Acinetobacter baumannii-induced endotoxemia. Our results reveal that SERPINB1 acts as a vital gatekeeper of inflammation by restraining neutrophil serine proteases and inflammatory caspases in a genetically and functionally separable manner.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biotechnology and Bioinformatics > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.