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Role of PARP‐1 in the modulation of neutrophil function: relevance for inflammatory bowel disease (902.5)
Author(s) -
Larmonier Claire,
Shehab Kareem,
McFadden RitaMarie,
Ghishan Fayez,
Kiela Pawel
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.902.5
Subject(s) - inflammatory bowel disease , parp1 , colitis , inflammation , immunology , immune system , neutrophil extracellular traps , poly adp ribose polymerase , chemotaxis , cancer research , medicine , biology , disease , biochemistry , enzyme , receptor , polymerase
Aberrant immune response has been proposed as the underlying cause of Inflammatory Bowel Diseases. Disease progression and relapse are attributed to a hyperactive adaptive immune response to the bowel luminal contents accompanied by a disproportionate and persistent neutrophil (PMN) influx. Poly(ADP‐ribose) polymerases (PARPs), including its most abundant isoform PARP1, catalyzes the transfer of ADP‐ribose units from NAD+ to a number of target proteins. In vivo studies have demonstrated that genetic ablation or pharmacological inhibition of PARP1 ameliorates the experimental colitis pathophysiological changes. Considering the essential role of PARP1 in the regulation of inflammation, we propose to evaluate the effect of Parp1 deletion on neutrophil function in a model of Dextran Sulfate Sodium (DSS)‐induced colitis. In comparison to WT mice, Parp1‐/‐ were protected from the effects of DSS, with significantly lower weight loss, and reduced proinflammatory mediators, including metalloproteinases and chemoattractants. The regulation of neutrophil‐related gene in the colon was also studied by microarray. Similarly, Parp1‐/‐ neutrophils demonstrated an impaired chemotaxis in vitro and reduced motility in vivo in a model of aseptic peritonitis. In light of these current findings, we postulate that the pathogenic role of PARP1 may be mediated in part by the regulation of neutrophil function. Grant Funding Source : Supported by NIH Grant 1K01DK099268‐01