RIPK2 as a New Therapeutic Target in Inflammatory Bowel Diseases.
RIPK2
inflammatory bowel diseases
nuclear factor-kappa B
pro-inflammatory cytokines
toll-like receptors
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
07
01
2021
accepted:
26
02
2021
entrez:
3
5
2021
pubmed:
4
5
2021
medline:
4
5
2021
Statut:
epublish
Résumé
Inflammatory bowel diseases (IBDs) are becoming more frequent worldwide. A significant fraction of patients with IBD are refractory to various types of therapeutic biologics and small molecules. Therefore, identification of novel therapeutic targets in IBD is required. Receptor-interacting serine/threonine kinase 2 (RIPK2), also known as receptor-interacting protein 2 (RIP2), is a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs). RIPK2 is expressed in antigen-presenting cells, such as dendritic cells and macrophages. Recognition of microbe-associated molecular patterns by NOD1, NOD2, and TLRs leads to the interaction between RIPK2 and these innate immune receptors, followed by the release of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23p40 through the activation of nuclear factor kappa B and mitogen-activated protein kinases. Thus, activation of RIPK2 plays a critical role in host defense against microbial infections. Recent experimental and clinical studies have provided evidence that activation of RIPK2 is involved in the development of autoimmune diseases, especially IBDs. In addition, the colonic mucosa of patients with IBD exhibits enhanced expression of RIPK2 and associated signaling molecules. Furthermore, the blockage of RIPK2 activation ameliorates the development of experimental murine colitis. Thus, activation of RIPK2 underlies IBD immunopathogenesis. In this review, we attempt to clarify the roles played by RIPK2 in the development of IBD by focusing on its associated signaling pathways. We also discuss the possibility of using RIPK2 as a new therapeutic target in IBD.
Identifiants
pubmed: 33935757
doi: 10.3389/fphar.2021.650403
pii: 650403
pmc: PMC8079979
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
650403Informations de copyright
Copyright © 2021 Honjo, Watanabe, Kamata, Minaga and Kudo.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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