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

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Madhi, RaedLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital (author)

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

Article/chapterEnglish2019

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2018-12-04
Wiley,2019

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LIBRIS-ID:oai:lup.lub.lu.se:d908f0e0-cdcf-4795-9b37-4fe9b99a1178
https://lup.lub.lu.se/record/d908f0e0-cdcf-4795-9b37-4fe9b99a1178URI
https://doi.org/10.1002/jcp.27874DOI

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Language:English
Summary in:English

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Recent evidence suggests that neutrophil extracellular traps (NETs) play an important role in the development of acute pancreatitis (AP). Herein, we examined the role of peptidylarginine deiminase (PAD), which has been shown to regulate NET formation, in severe AP. AP was induced by retrograde of taurocholate infusion into pancreatic duct in C57BL/6 mice. PAD was pharmacologically inhibited using Cl-amidine, a pan-PAD inhibitor. Pancreata were collected, and histones, citrullinated histone 3, chemokines, myeloperoxidase, and NETs were quantified. Chemokines, matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and DNA-histone complexes were determined in plasma samples. Infusion of taurocholate induced formation of NETs in pancreatic tissues of mice. Pretreatment with Cl-amidine markedly reduced the NET formation in the inflamed pancreas. Moreover, inhibition of PAD decreased the levels of blood amylase as well as edema, acinar cell necrosis, hemorrhage, and neutrophil infiltration in the pancreas of animals with AP. Administration of Cl-amidine attenuated the myeloperoxidase levels in the pancreas and lung of mice exposed to taurocholate. In addition, Cl-amidine decreased pancreatic levels of CXC chemokines, plasma levels of IL-6, and MMP-9 in mice with severe AP. This study shows that Cl-amidine is a potent inhibitor of NET formation in severe AP. Also, our results suggest that PAD regulates pathological inflammation and tissue damage in the inflamed pancreas. Thus, targeting PAD might be a useful strategy to treat patients with severe AP.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
chemokines
histones
inflammation
leukocyte and pancreas

Added entries (persons, corporate bodies, meetings, titles ...)

Rahman, MilladurLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-mdr (author)
Taha, DlerLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups(Swepub:lu)dl0400ta (author)
Mörgelin, MatthiasLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)medk-mmn (author)
Thorlacius, HenrikLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kir-hth (author)
KirurgiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:Journal of Cellular Physiology: Wiley234:7, s. 11850-118600021-95411097-4652

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