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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

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    Authors
    Mishra, Neha
    Schwerdtner, Lidja
    Sams, Kelly
    Mondal, Santanu
    Ahmad, Fareed
    Schmidt, Reinhold E.
    Coonrod, Scott A.
    Thompson, Paul R
    Lerch, Markus M.
    Bossaller, Lukas
    UMass Chan Affiliations
    Thompson Lab
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2019-08-15
    Keywords
    Protein arginine deiminase
    PAD enzymes
    citrulline
    protein citrullination
    pyroptosis
    macrophages
    Cl-amidine
    NLRP3 inflammasome
    Amino Acids, Peptides, and Proteins
    Biochemistry
    Enzymes and Coenzymes
    Immunology and Infectious Disease
    Medicinal-Pharmaceutical Chemistry
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    Link to Full Text
    https://doi.org/10.4049/jimmunol.1800720
    Abstract
    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.
    Source

    J Immunol. 2019 Aug 15;203(4):795-800. doi: 10.4049/jimmunol.1800720. Epub 2019 Jul 10.

    DOI
    10.4049/jimmunol.1800720
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/46423
    PubMed ID
    31292215
    Related Resources

    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.1800720
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