Caspase-11, a specific sensor for intracellular lipopolysaccharide recognition, mediates the non-canonical inflammatory pathway of pyroptosis

Abstract

Pyroptosis, a type of programmed cell death that along with inflammation, is mainly regulated by two main pathways, cysteinyl aspartate specific proteinase (caspase)-1-induced canonical inflammatory pathway and caspase-11-induced non-canonical inflammatory pathway. The non-canonical inflammatory pathway-induced pyroptosis is a unique immune response in response to gram-negative (G − ) bacteria. It is induced by lipopolysaccharide (LPS) on the surface of G − bacteria. This activates caspase-11 which, in turn, activates a series of downstream proteins eventually forming protein pores on the cell membrane and inducing cell sacrificial processes. Caspase-11 belongs to the caspase family and is an homologous protein of caspase-1. It has the ability to specifically hydrolyze proteins, but it is still unclear how it regulates cell death caused by non-canonical inflammatory pathways. The present study describes a pathway that enables LPS to directly enter the cell and activate caspase-11, and the key role caspase-11 plays in the activation of pyroptosis and inflammation.

Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1

“…In addition to the canonical NLRP3 inflammasome activation, there is another noncanonical activation that targets caspase‐11, which directly induce canonical NLRP3 inflammasome activation by binding NF‐κB, leading to the proteolysis and activation of pro‐caspase‐1 to form active caspase‐1 dimers 50,51 . Additionally, activated caspase‐11‐dependent noncanonical inflammasome can cleave the linker loop of gasdermin D (GSDMD), resulting in cell swelling and rupture, known as pyroptosis 52–54 . PF treatment significantly suppressed the expression of caspase‐11 (Fig.…”

Recent Advances in Lipopolysaccharide Recognition Systems

“…Over a decade ago, caspase-1 and caspase-11 were thought to contribute similar signaling pathways in inflammation due to the fact of their highly homologous sequences [101,102]. Further supporting this hypothesis, in vivo studies with caspase-1 (Casp1-/-) and caspase-11 (Casp11-/-) knockout mice demonstrated that both were resistant to endotoxin shock induced by LPS when compared to wild-type mice [103,104].…”

Reactive Glia Inflammatory Signaling Pathways and Epilepsy

“…The decrease in intracellular K+ activates then NLRP3, producing IL-1β and IL-18 that are released from the cell throughout the gasdermin-N pores. Eventually, cells die by pyroptosis [15,52,59] ( Figure 2).…”