Mutual Regulation of TLR/NLR and CEACAM1 in the Intestinal Microvasculature: Implications for IBD Pathogenesis and Therapy.
Animals
Antigens, Bacterial
/ immunology
Antigens, CD
/ genetics
Case-Control Studies
Cell Adhesion Molecules
/ antagonists & inhibitors
Cell Movement
Cell Proliferation
Cytokines
/ metabolism
Humans
Immunity, Innate
/ immunology
Inflammation Mediators
/ metabolism
Inflammatory Bowel Diseases
/ drug therapy
Intestinal Mucosa
/ immunology
Mice
Mice, Inbred BALB C
Microvessels
/ immunology
Neovascularization, Physiologic
Nod1 Signaling Adaptor Protein
/ metabolism
Nod2 Signaling Adaptor Protein
/ metabolism
RNA, Small Interfering
/ genetics
Toll-Like Receptor 2
/ metabolism
Toll-Like Receptor 4
/ metabolism
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
10 01 2019
10 01 2019
Historique:
received:
10
06
2018
pubmed:
9
10
2018
medline:
7
1
2020
entrez:
9
10
2018
Statut:
ppublish
Résumé
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) displays multiple activities, among which pathogen binding and angiogenesis are particularly prominent. These same functions are also exerted by Toll- and NOD-like receptors (TLRs and NLRs), which are critical mediators of innate immune responses. We investigated whether a functional inter-relationship exists between CEACAM1 and TLRs and NLRs and its potential impact on induction of intestinal angiogenesis. This hypothesis was tested using human intestinal microvascular endothelial cells, a unique cell population exposed to microbial products under physiological and pathological conditions. The results show that activation of TLR2/4, TLR4, NOD1, and NOD2 by specific bacterial ligands selectively and differentially upregulates the levels of cellular and soluble CEACAM1 produced by intestinal microvascular endothelial cells. The results also show that CEACAM1 regulates the migration, transmigration, and tube formation of these endothelial cells and mediates vessel sprouting induced by specific TLR and NLR bacterial ligands. Combined, these results demonstrate a close and reciprocal regulatory interaction between CEACAM1 and bacterial products in mediating multiple functions essential to new vessel formation in the gut mucosa. A coordinated and reciprocal interaction of CEACAM1 and microbiota-derived factors is necessary to optimize angiogenesis in the gut mucosa. This suggests that a coordination of endogenous and exogenous innate immune responses is necessary to promote intestinal angiogenesis under physiological and inflammatory conditions such as inflammatory bowel disease.
Sections du résumé
Background
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) displays multiple activities, among which pathogen binding and angiogenesis are particularly prominent. These same functions are also exerted by Toll- and NOD-like receptors (TLRs and NLRs), which are critical mediators of innate immune responses. We investigated whether a functional inter-relationship exists between CEACAM1 and TLRs and NLRs and its potential impact on induction of intestinal angiogenesis.
Methods
This hypothesis was tested using human intestinal microvascular endothelial cells, a unique cell population exposed to microbial products under physiological and pathological conditions.
Results
The results show that activation of TLR2/4, TLR4, NOD1, and NOD2 by specific bacterial ligands selectively and differentially upregulates the levels of cellular and soluble CEACAM1 produced by intestinal microvascular endothelial cells. The results also show that CEACAM1 regulates the migration, transmigration, and tube formation of these endothelial cells and mediates vessel sprouting induced by specific TLR and NLR bacterial ligands. Combined, these results demonstrate a close and reciprocal regulatory interaction between CEACAM1 and bacterial products in mediating multiple functions essential to new vessel formation in the gut mucosa.
Conclusions
A coordinated and reciprocal interaction of CEACAM1 and microbiota-derived factors is necessary to optimize angiogenesis in the gut mucosa. This suggests that a coordination of endogenous and exogenous innate immune responses is necessary to promote intestinal angiogenesis under physiological and inflammatory conditions such as inflammatory bowel disease.
Identifiants
pubmed: 30295747
pii: 5116171
doi: 10.1093/ibd/izy316
pmc: PMC6327233
doi:
Substances chimiques
Antigens, Bacterial
0
Antigens, CD
0
CD66 antigens
0
Cell Adhesion Molecules
0
Cytokines
0
Inflammation Mediators
0
NOD1 protein, human
0
NOD2 protein, human
0
Nod1 Signaling Adaptor Protein
0
Nod2 Signaling Adaptor Protein
0
RNA, Small Interfering
0
TLR2 protein, human
0
TLR4 protein, human
0
Toll-Like Receptor 2
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
294-305Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK110415
Pays : United States
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