Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.
Animals
Cecum
/ metabolism
Colitis
/ chemically induced
Crohn Disease
/ metabolism
Duodenitis
/ chemically induced
Duodenum
/ metabolism
Gene Expression
Humans
Ileitis
/ chemically induced
Ileum
/ metabolism
Interferon-gamma
/ metabolism
Interleukin-12
/ metabolism
Intestinal Mucosa
/ metabolism
Mice
Mice, Knockout
Nod2 Signaling Adaptor Protein
/ genetics
RNA, Messenger
/ metabolism
Trinitrobenzenesulfonic Acid
Tumor Necrosis Factor-alpha
/ metabolism
CD4+ T cells
Crohn’s disease
Nod2
gut barrier
inflammatory cytokines
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
19 Jun 2020
19 Jun 2020
Historique:
pubmed:
1
12
2019
medline:
15
4
2021
entrez:
1
12
2019
Statut:
ppublish
Résumé
Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known. We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS]. In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum. Nod2 protects the gut from colitis spreading to small intestine.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known.
METHODS
METHODS
We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS].
RESULTS
RESULTS
In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum.
CONCLUSIONS
CONCLUSIONS
Nod2 protects the gut from colitis spreading to small intestine.
Identifiants
pubmed: 31784737
pii: 5648102
doi: 10.1093/ecco-jcc/jjz196
doi:
Substances chimiques
NOD2 protein, human
0
Nod2 Signaling Adaptor Protein
0
Nod2 protein, mouse
0
RNA, Messenger
0
Tumor Necrosis Factor-alpha
0
Interleukin-12
187348-17-0
Interferon-gamma
82115-62-6
Trinitrobenzenesulfonic Acid
8T3HQG2ZC4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
669-679Informations de copyright
Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.