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.
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.