Back to Search
Start Over
Cathepsin B regulates non‐canonical NLRP3 inflammasome pathway by modulating activation of caspase‐11 in Kupffer cells.
- Source :
- Cell Proliferation; Dec2018, Vol. 51 Issue 6, pN.PAG-N.PAG, 1p
- Publication Year :
- 2018
-
Abstract
- Objectives: The non‐canonical inflammasome pathway was described which engages caspase‐11 to mediate pyroptosis and the subsequent release of IL‐1α, IL‐1β and IL‐18 in TLR4‐independent way. Cathepsin B is capable of activating caspase‐11 under cell‐free conditions which may regulate non‐canonical NLRP3 inflammasome pathway. In this study, we aimed to further investigate cathepsin B as potential activators of proinflammatory caspases which may be released upon proinflammatory stimuli and regulate non‐canonical NLRP3 inflammasome pathway by modulating the activity of caspase‐11. Methods: Pharmacological and gene‐silencing approaches were used to evaluate the impact of cathepsin B on regulating non‐canonical NLRP3 inflammasome pathway in wild‐type and TLR4–/– Kupffer cells. A sepsis model was also created to investigate the effect of cathepsin B on survival. Meanwhile, cathepsin B activity and the expression level of caspase‐4 were detected in human peripheral blood mononuclear cells (PBMC) which were separated from patients suffered from SIRS or sepsis and healthy volunteers. Results: LPS stimulation caused cathepsin B activity and caspase‐11 expression increase in TLR4–/– mice. Cathepsin B activity inhibition reduced the activation of caspase‐11 and inflammasome and benefited survival in TLR4–/– mice. Upregulation of cathepsin B activity and caspase‐4 activation was found in PBMC of patients with SIRS or sepsis. Conclusion: Our results suggest a critical role for cathepsin B as activators of proinflammatory caspases‐11 and the regulatory effect in LPS‐induced caspases‐11‐dependent necrosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- CATHEPSIN B
INFLAMMASOMES
CASPASES
KUPFFER cells
PHARMACOLOGY
GENE silencing
Subjects
Details
- Language :
- English
- ISSN :
- 09607722
- Volume :
- 51
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Cell Proliferation
- Publication Type :
- Academic Journal
- Accession number :
- 133048186
- Full Text :
- https://doi.org/10.1111/cpr.12487