Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation

Jesus Cosin-Roger, Simona Simmen, Hassan Melhem, Kirstin Atrott, Isabelle Frey-Wagner, Martin Hausmann, Cheryl de Vallière, Marianne R. Spalinger, Patrick Spielmann, Roland H. Wenger, Jonas Zeitz, Stephan R. Vavricka, Gerhard Rogler and Pedro A. Ruiz ()
Additional contact information
Jesus Cosin-Roger: University Hospital Zurich, University of Zurich
Simona Simmen: University Hospital Zurich, University of Zurich
Hassan Melhem: University Hospital Zurich, University of Zurich
Kirstin Atrott: University Hospital Zurich, University of Zurich
Isabelle Frey-Wagner: University Hospital Zurich, University of Zurich
Martin Hausmann: University Hospital Zurich, University of Zurich
Cheryl de Vallière: University Hospital Zurich, University of Zurich
Marianne R. Spalinger: University Hospital Zurich, University of Zurich
Patrick Spielmann: University of Zurich
Roland H. Wenger: University of Zurich
Jonas Zeitz: University Hospital Zurich, University of Zurich
Stephan R. Vavricka: University Hospital Zurich, University of Zurich
Gerhard Rogler: University Hospital Zurich, University of Zurich
Pedro A. Ruiz: University Hospital Zurich, University of Zurich

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Hypoxia regulates autophagy and nucleotide-binding oligomerization domain receptor, pyrin domain containing (NLRP)3, two innate immune mechanisms linked by mutual regulation and associated to IBD. Here we show that hypoxia ameliorates inflammation during the development of colitis by modulating autophagy and mammalian target of rapamycin (mTOR)/NLRP3 pathway. Hypoxia significantly reduces tumor necrosis factor α, interleukin (IL)-6 and NLRP3 expression, and increases the turnover of the autophagy protein p62 in colon biopsies of Crohn’s disease patients, and in samples from dextran sulfate sodium-treated mice and Il-10 −/− mice. In vitro, NF-κB signaling and NLRP3 expression are reduced through hypoxia-induced autophagy. We also identify NLRP3 as a novel binding partner of mTOR. Dimethyloxalylglycine-mediated hydroxylase inhibition ameliorates colitis in mice, downregulates NLRP3 and promotes autophagy. We suggest that hypoxia counteracts inflammation through the downregulation of the binding of mTOR and NLRP3 and activation of autophagy.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00213-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00213-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00213-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().