Affordable Access

deepdyve-link
Publisher Website

Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer.

Authors
  • Stettner, Noa1
  • Rosen, Chava2
  • Bernshtein, Biana3
  • Gur-Cohen, Shiri3
  • Frug, Julia4
  • Silberman, Alon4
  • Sarver, Alona4
  • Carmel-Neiderman, Narin N4
  • Eilam, Raya5
  • Biton, Inbal5
  • Pevsner-Fischer, Meirav3
  • Zmora, Niv3
  • Brandis, Alexander6
  • Bahar Halpern, Keren7
  • Mazkereth, Ram8
  • di Bernardo, Diego9
  • Brunetti-Pierri, Nicola10
  • Premkumar, Muralidhar H11
  • Dank, Gillian12
  • Nagamani, Sandesh C S13
  • And 3 more
  • 1 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel; Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel; Koret School of Veterinary Medicine, Hebrew University, Rehovot, Israel. , (Israel)
  • 2 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; The Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel. , (Israel)
  • 3 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. , (Israel)
  • 4 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel. , (Israel)
  • 5 Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel. , (Israel)
  • 6 Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel. , (Israel)
  • 7 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. , (Israel)
  • 8 The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. , (Israel)
  • 9 Telethon Institute of Genetics and Medicine, Pozzuoli, Italy; Department of Chemical, Materials and Industrial Engineering, Federico II University, Naples, Italy. , (Italy)
  • 10 Telethon Institute of Genetics and Medicine, Pozzuoli, Italy; Department of Translational Medicine, Federico II University, Naples, Italy. , (Italy)
  • 11 Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA.
  • 12 Koret School of Veterinary Medicine, Hebrew University, Rehovot, Israel. , (Israel)
  • 13 Texas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
  • 14 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel. Electronic address: [email protected] , (Israel)
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
May 15, 2018
Volume
23
Issue
7
Pages
1962–1976
Identifiers
DOI: 10.1016/j.celrep.2018.04.053
PMID: 29768197
Source
Medline
Keywords
License
Unknown

Abstract

Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation. We find that induction of endogenous NO production by enterocytes with supplements that upregulate ASL expression and complement its substrates results in improved epithelial integrity and alleviation of colitis and of inflammation-associated colon cancer.

Report this publication

Statistics

Seen <100 times