Caspase-8-mediated CYLD cleavage boosts LPS-induced endotoxic shock - PubMed
5 hours ago
- #endotoxic shock
- #Caspase-8
- #CYLD cleavage
- Caspase-8 plays a significant role in cytokine production during septic shock.
- Mice with a specific CYLD mutation (CyldD215A/D215A) showed protection against lethal endotoxic shock.
- Deletion of Cyld in Caspase8-/-Mlkl-/- mice restored sensitivity to endotoxic shock.
- Caspase-8 promotes endotoxic shock by cleaving and degrading CYLD, removing its anti-inflammatory function.
- CYLD removes LUBAC-mediated M1-linked ubiquitination of p65 at K301/K303, suppressing NF-κB-driven inflammatory responses.
- The CYLD D215A mutation resists Caspase-8-mediated cleavage, exerting anti-inflammatory effects.
- CYLD cleavage is a promising therapeutic target for combating inflammation in endotoxic shock.