Inhibition of RIPK3 Pathway Attenuates Intestinal Inflammation and Cell Death of Inflammatory Bowel Disease and Suppresses Necroptosis in Peripheral Mononuclear Cells of Ulcerative Colitis Patients.
Inflammation
Inflammatory bowel diseases
Necroptosis
RIPK3 protein
Ulcerative colitis
Journal
Immune network
ISSN: 1598-2629
Titre abrégé: Immune Netw
Pays: Korea (South)
ID NLM: 101137270
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
27
09
2019
revised:
03
01
2020
accepted:
09
01
2020
entrez:
13
5
2020
pubmed:
13
5
2020
medline:
13
5
2020
Statut:
epublish
Résumé
Receptor-interacting serine/threonine-protein kinase (RIPK) 3 is a member of the TNF receptor-I signaling complex and mediates necroptosis, an inflammatory cell death. Ulcerative colitis (UC) is an excessive inflammatory disease caused by uncontrolled T cell activation. The current study is aimed to determine whether RIPK3 inhibitor attenuates UC development inhibiting inflammation and necroptosis using experimental colitis mice model. Dextran sulfate sodium-induced colitis mice were administered RIPK3 inhibitor (3 mg/ml) 3 times and their tissues were analyzed by immunohistochemistry. RIPK3, mixed lineage kinase domain-like (MLKL), phosphorylated MLKL, IL-17, and CD4 in colitis patient colon tissues were detected using confocal microscopy. Protein levels were measured using immunohistochemistry and ELISA. The differentiation of Th17 cells was evaluated using flow cytometry. The expression of proinflammatory cytokines and necroptosis in peripheral blood mononuclear cells from UC patients was decreased markedly by RIPK3 inhibitor treatment. We also observed that the injection of RIPK3 inhibitor improves colitis severity and protects intestinal destruction. RIPK3 inhibitor reduced necroptosis factors and proinflammatory cytokines in the colon and consequently protected colon devastation. The expression of inflammatory mediators in experimental colitis mice splenocytes was decreased significantly by RIPK3 inhibitor treatment. These results suggest that RIPK3 inhibitor ameliorates severity of experimental colitis and reduces inflammation through the inhibition of inflammatory response and necroptosis and support RIPK3-targeting substances for treatment of UC.
Identifiants
pubmed: 32395368
doi: 10.4110/in.2020.20.e16
pmc: PMC7192830
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e16Informations de copyright
Copyright © 2020. The Korean Association of Immunologists.
Déclaration de conflit d'intérêts
Conflicts of Interest: The authors declare no potential conflicts of interest.
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