PARP-1 regulates inflammasome activity by poly-ADP-ribosylation of NLRP3 and interaction with TXNIP in primary macrophages

• DOI: 10.1007/s00018-022-04138-z
• Publication Date: 2022-01-30T18:02:20Z
• Authors: Ling-Ya Chiu; Duen-Yi Huang; Wan-Wan Lin
• Keywords: AIM2; Pyroptosis

Abstract Poly(ADP-ribose) polymerase-1 (PARP-1) plays an essential role in DNA repair by catalyzing the polymerization of ADP-ribose unit to target proteins. Several studies have shown that PARP-1 can regulate inflammatory responses various disease models. The intracellular Nod-like receptor NLRP3 has emerged as most crucial innate immune because its broad specificity mediating response pathogen invasion and danger signals associated with cellular damage. In our study, we found stimuli-induced caspase-1 maturation IL-1β production were impaired knockout or inhibition bone marrow-derived macrophages (BMDM). step 1 signal inflammasome activation was not affected deficiency. Moreover, ATP-induced cytosolic ROS lower Parp-1 −/− BMDM, resulting decreased complex assembly. translocate cytosol upon ATP stimulation trigger PARylation modification on NLRP3, leading also a bridge between thioredoxin-interacting protein (TXNIP) participated NLRP3/TXNIP formation for activation. Overall, positively regulates via increasing interaction TXNIP NLRP3. Our data demonstrate novel regulatory mechanism PARP-1. Therefore, serve potential treatment diseases.