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Necroptosis is active in children with inflammatory bowel disease and contributes to heighten intestinal inflammation.
- Source :
-
The American journal of gastroenterology [Am J Gastroenterol] 2014 Feb; Vol. 109 (2), pp. 279-87. Date of Electronic Publication: 2013 Dec 10. - Publication Year :
- 2014
-
Abstract
- Objectives: A new caspase-independent mode of programmed cell death, termed necroptosis, has recently been identified. Altered expression of molecules involved in the necroptosis pathway has been shown to trigger intestinal inflammation. The initiation of necroptosis is principally mediated by the release of receptor interacting protein 3 (RIP3) from suppression by caspase-8. Furthermore, it has been suggested that the mixed lineage kinase domain-like (MLKL) factor is an interacting target of RIP3 in active necroptosis. This study aims at investigating the occurrence of necroptosis in children with inflammatory bowel disease (IBD) and its contribution to human intestinal inflammation.<br />Methods: Biopsy samples were collected from the ileum and colon of 33 children with Crohn's disease, 30 with ulcerative colitis, and 20 healthy controls. Ten children with allergic colitis (AC) were used as non-IBD comparators. RIP3, caspase-8, and MLKL protein expression levels were evaluated by western blotting. The adenocarcinoma cell line HT29 was used for in vitro experiments.<br />Results: RIP3 and MLKL increased (P<0.01) in inflamed tissues of IBD and AC patients, whereas caspase-8 was reduced. No variations were observed in uninflamed tissues of patients. The relationship between RIP3 increase, active necroptosis, and intestinal inflammation was confirmed by in vitro analyses.<br />Conclusions: We show for the first time that necroptosis is strongly associated with intestinal inflammation in children with IBD and contributes to strengthen the inflammatory process. We believe that RIP3 and MLKL could represent attractive targets for the management of human IBD.
- Subjects :
- Adolescent
Age Factors
Biopsy, Needle
Blotting, Western
Cell Survival
Child
Child, Preschool
Cohort Studies
Colitis, Ulcerative genetics
Colitis, Ulcerative pathology
Colitis, Ulcerative physiopathology
Colon pathology
Crohn Disease genetics
Crohn Disease pathology
Crohn Disease physiopathology
Disease Progression
Female
Gene Expression Regulation
Humans
Ileum pathology
Immunohistochemistry
Inflammatory Bowel Diseases pathology
Inflammatory Bowel Diseases physiopathology
Male
Prospective Studies
Real-Time Polymerase Chain Reaction
Risk Assessment
Severity of Illness Index
Signal Transduction
Statistics, Nonparametric
Caspase 8 metabolism
Cell Death genetics
Inflammatory Bowel Diseases genetics
Protein Kinases genetics
Receptor-Interacting Protein Serine-Threonine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1572-0241
- Volume :
- 109
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 24322838
- Full Text :
- https://doi.org/10.1038/ajg.2013.403