Cul4B tags NLRP3 for ubiquitination and shields the lung in sepsis models
- Cul4B fell in the lungs of two sepsis-induced acute lung injury mouse models; lung overexpression limited injury and inflammation, while myeloid-specific deletion worsened barrier damage.
- Cul4B bound NLRP3 and promoted its ubiquitination, restraining inflammasome activation in THP-1 cells and in Cul4B-deficient macrophages.
- MN-08, a small molecule reported earlier to protect against LPS-induced lung injury, raised Cul4B expression and suppressed NLRP3.
💡 Points Based on the abstract
An E3 scaffold that naturally removes NLRP3 is an appealing node, but raising a scaffold's expression pharmacologically is much harder than inhibiting an enzyme. How selective MN-08 is for Cul4B is the open question. So is whether protection survives when treatment starts after sepsis onset, the only setting that matters clinically, rather than as prophylaxis.