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Cutting Edge: Protein Arginine Deiminase 2 and 4 Regulate NLRP3 Inflammasome-Dependent IL-1β Maturation and ASC Speck Formation in Macrophages

Protein arginine deiminase (PAD) enzymes catalyze the conversion of protein-bound arginine into citrulline, an irreversible posttranslational modification with loss of a positive charge that can influence protein-protein interactions and protein structure. Protein arginine deiminase activity depends...

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Main Authors: Mishra, Neha (Author) , Schwerdtner, Lidja (Author) , Sams, Kelly (Author) , Mondal, Santanu (Author) , Ahmad, Fareed (Author) , Schmidt, Reinhold E. (Author) , Coonrod, Scott A. (Author) , Thompson, Paul R. (Author) , Lerch, Markus M. (Author) , Bossaller, Lukas Friedrich Magnus (Author)
Format: Article (Journal)
Language:English
Published: 10 July 2019
In: The journal of immunology
Year: 2019, Volume: 203, Issue: 4, Pages: 795-800
ISSN:1550-6606
DOI:10.4049/jimmunol.1800720
Online Access:Verlag, Volltext: https://doi.org/10.4049/jimmunol.1800720
Verlag, Volltext: https://www.jimmunol.org/content/203/4/795
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Author Notes:Neha Mishra, Lidja Schwerdtner, Kelly Sams, Santanu Mondal, Fareed Ahmad, Reinhold E. Schmidt, Scott A. Coonrod, Paul R. Thompson, Markus M. Lerch, Lukas Bossaller
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Summary:Protein arginine deiminase (PAD) enzymes catalyze the conversion of protein-bound arginine into citrulline, an irreversible posttranslational modification with loss of a positive charge that can influence protein-protein interactions and protein structure. Protein arginine deiminase activity depends on high intracellular calcium concentrations occurring in dying cells. In this study, we demonstrate that protein citrullination is common during pyroptotic cell death in macrophages and that inhibition of PAD enzyme activity by Cl-amidine, a pan-PAD inhibitor, blocks NLRP3 inflammasome assembly and proinflammatory IL-1β release in macrophages. Genetic deficiency of either PAD2 or PAD4 alone in murine macrophages does not impair IL-1β release; however, pharmacological inhibition or small interfering RNA knockdown of PAD2 within PAD4−/− macrophages does. Our results suggest that PAD2 and 4 activity in macrophages is required for optimal inflammasome assembly and IL-1β release, a finding of importance for autoimmune diseases and inflammation.
Item Description:Prepublished online 10 July 2019
Gesehen am 21.04.2020
Physical Description:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.1800720

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