Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation
Huw D. Lewis,John Liddle,Jim E Coote,Stephen John Atkinson,Michael David Barker,Benjamin D. Bax,Kevin L. Bicker,Ryan P. Bingham,Matthew Campbell,Yu Hua Chen,Chun-wa Chung,Peter D. Craggs,Robert P. Davis,Dirk Eberhard,Gerard Joberty,Kenneth E Lind,Kelly Locke,Claire Maller,Kimberly Martinod,Chris Patten,Oxana Polyakova,Cecil E Rise,Martin Rüdiger,Robert J. Sheppard,Daniel J. Slade,Pamela Thomas,Jim Thorpe,Gang Yao,Gerard Drewes,Denisa D. Wagner,Paul R. Thompson,Rab K. Prinjha,David Matthew Wilson +32 more
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Novel, selective PAD4 inhibitors binding to a calcium-deficient form of the PAD3 enzyme have been validated, for the first time, in both histone citrullination and neutrophil extracellular trap formation, validating the critical enzymatic role of human and mouse PAD 4.Abstract:
PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored.read more
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Neutrophil extracellular traps in immunity and disease
TL;DR: The identification of molecules that modulate the release of NETs has helped to refine the view of the role of neutrophils in immune protection, inflammatory and autoimmune diseases and cancer.
Journal ArticleDOI
Pathogenetic insights from the treatment of rheumatoid arthritis.
Iain B. McInnes,Georg Schett +1 more
TL;DR: It becomes apparent that understanding the effects of specific immune interventions can elucidate definitive molecular or cellular nodes that are essential to maintain complex inflammatory networks that subserve diseases like rheumatoid arthritis.
Journal ArticleDOI
An emerging role for neutrophil extracellular traps in noninfectious disease
Selina K. Jorch,Paul Kubes +1 more
TL;DR: The role of NETosis in autoimmunity, coagulation, acute injuries and cancer, and whether extracellular DNA is always detrimental in sterile inflammation are described.
Journal ArticleDOI
Diabetes primes neutrophils to undergo NETosis, which impairs wound healing
Siu Ling Wong,Melanie Demers,Kimberly Martinod,Maureen Gallant,Yanming Wang,Allison B. Goldfine,C. Ronald Kahn,Denisa D. Wagner +7 more
TL;DR: It is shown that neutrophils isolated from type 1 and type 2 diabetic humans and mice were primed to produce NETs (a process termed NETosis), and wound healing was accelerated in Padi4−/− mice as compared to WT mice, and it was not compromised by diabetes.
Journal ArticleDOI
Diverse stimuli engage different neutrophil extracellular trap pathways
Elaine F. Kenny,Alf Herzig,Renate Krüger,Aaron Muth,Santanu Mondal,Paul R. Thompson,Volker Brinkmann,Horst von Bernuth,Arturo Zychlinsky +8 more
TL;DR: It is demonstrated that NETosis occurs through several signalling mechanisms, suggesting that extrusion of NETs is important in host defence.
References
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