Isocyanic acid-mediated NLRP3 carbamoylation reduces NLRP3-NEK7 interaction and limits inflammasome activation.

ABSTRACT: Isocyanic acid, as a reactive metabolite synthesized by the enzyme LACC1, can carbamoylate the ε-amino group of lysine residues in proteins. However, the role of isocyanic acid in inflammatory response remains elusive. Herein, we reveal that lipopolysaccharide stimulation increases LACC1-dependent isocyanic acid production, which attenuates inflammation by limiting the NLRP3 inflammasome activation in macrophages primed with lipopolysaccharide for 8 hours. Mechanistically, isocyanic acid directly carbamoylates NLRP3 at lysine-593 to disrupt NLRP3-NEK7 interaction, a key step in assembly of active NLRP3 inflammasome. Abrogation of isocyanic acid biosynthesis by LACC1/Lacc1 knockout or expression of K593 carbamoylation (K593ca)-deficient NLRP3 mutant promotes macrophagic inflam

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC11887815 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature