- Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation.
Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation.
Nature communications (2017-07-26)
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, Pedro A Ruiz
PMID28740109
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