ArticleImmunoHorizons2024
Poly(ADP-Ribose) Polymerase-1 Regulates Pyroptosis Independent Function of NLRP3 Inflammasome in Neutrophil Extracellular Trap Formation.
Article in ImmunoHorizons, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Cleavage and inactivation of poly(ADP-ribose) polymerase in peripheral blood mononuclear cells of patients with acute respiratory distress syndrome.Respiratory research · 2026Article
- GSDMD deficiency attenuates BPD by suppressing macrophage pyroptosis and promoting M2 polarization.Cell death discovery · 2025Article
- PARP Inhibition Shifts Murine Myeloid Cells Toward a More Tolerogenic Profile In Vivo.Biomolecules · 2025Article
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9 authors.
Funding
Abstract
Neutrophil extracellular traps (NETs) function to control infectious agents as well as to propagate inflammatory response in a variety of disease conditions. DNA damage associated with chromatin decondensation and NACHT domain-leucine-rich repeat-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation have emerged as crucial events in NET formation, but the link between the two processes is unknown. In this study, we demonstrate that poly(ADP-ribose) polymerase-1 (PARP-1), a key DNA repair enzyme, regulates NET formation triggered by NLRP3 inflammasome activation in neutrophils. Activation of mouse neutrophils with canonical NLRP3 stimulants LPS and nigericin induced NET formation, which was significantly abrogated by pharmacological inhibition of PARP-1. We found that PARP-1 is required for NLRP3 inflammasome assembly by regulating post-transcriptional levels of NLRP3 and ASC dimerization. Importantly, this PARP-1-regulated NLRP3 activation for NET formation was independent of inflammasome-mediated pyroptosis, because caspase-1 and gasdermin D processing as well as IL-1β transcription and secretion remained intact upon PARP-1 inhibition in neutrophils. Accordingly, pharmacological inhibition or genetic ablation of caspase-1 and gasdermin D had no effect on NLRP3-mediated NET formation. Mechanistically, PARP-1 inhibition increased p38 MAPK activity, which was required for downmodulation of NLRP3 and NETs, because concomitant inhibition of p38 MAPK with PARP-1 restored NLRP3 activation and NET formation. Finally, mice undergoing bacterial peritonitis exhibited increased survival upon treatment with PARP-1 inhibitor, which correlated with increased leukocyte influx and improved intracellular bacterial clearance. Our findings reveal a noncanonical pyroptosis-independent role of NLRP3 in NET formation regulated by PARP-1 via p38 MAPK, which can be targeted to control NETosis in inflammatory diseases.
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