Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis

2018 ◽  
Vol 234 (7) ◽  
pp. 11850-11860 ◽  
Author(s):  
Raed Madhi ◽  
Milladur Rahman ◽  
Dler Taha ◽  
Matthias Mörgelin* ◽  
Henrik Thorlacius
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Tissue Injury ◽  
Neutrophil Extracellular Trap ◽  
Peptidylarginine Deiminase ◽  
Trap Formation ◽  
Extracellular Trap

scholarly journals Role of Peptidylarginine Deiminase 4 in Neutrophil Extracellular Trap Formation and Host Defense during Klebsiella pneumoniae–Induced Pneumonia-Derived Sepsis

2018 ◽  
Vol 201 (4) ◽  
pp. 1241-1252 ◽  
Author(s):  
Theodora A. M. Claushuis ◽  
Lieve E. H. van der Donk ◽  
Anna L. Luitse ◽  
Henk A. van Veen ◽  
Nicole N. van der Wel ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Host Defense ◽  
Neutrophil Extracellular Trap ◽  
Peptidylarginine Deiminase ◽  
Peptidylarginine Deiminase 4 ◽  
Trap Formation ◽  
Extracellular Trap

scholarly journals TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qian Ou ◽  
Jia-qi Fang ◽  
Zhe-sheng Zhang ◽  
Zhe Chi ◽  
Jie Fang ◽  
...  
Keyword(s):  
Innate Immune ◽  
Neutrophil Extracellular Trap ◽  
Mrna Levels ◽  
Peptidylarginine Deiminase ◽  
E Coli ◽  
Peptidylarginine Deiminase 4 ◽  
Trap Formation ◽  
Extracellular Trap ◽  
Innate Immune Evasion

AbstractTcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-type E. coli CFT073 (CFT073wt) and LPS-induced in vitro NETosis with CFT073wt or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.

Extracellular cold-inducible RNA-binding protein regulates neutrophil extracellular trap formation and tissue damage in acute pancreatitis

2020 ◽  
Vol 100 (12) ◽  
pp. 1618-1630
Author(s):  
Johan Linders ◽  
Raed Madhi ◽  
Milladur Rahman ◽  
Matthias Mörgelin ◽  
Sara Regner ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Tissue Damage ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Neutrophil Extracellular Trap ◽  
Trap Formation ◽  
Extracellular Trap

scholarly journals Peptidylarginine Deiminase Inhibitor Suppresses Neutrophil Extracellular Trap Formation and MPO-ANCA Production

2016 ◽  
Vol 7 ◽  
Author(s):  
Yoshihiro Kusunoki ◽  
Daigo Nakazawa ◽  
Haruki Shida ◽  
Fumihiko Hattanda ◽  
Arina Miyoshi ◽  
...  
Keyword(s):  
Neutrophil Extracellular Trap ◽  
Peptidylarginine Deiminase ◽  
Trap Formation ◽  
Extracellular Trap
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