Leukocyte Apheresis Using a Fiber Filter Suppresses Colonic Injury Through Calcitonin Gene-Related Peptide Induction.
Animals
Calcitonin Gene-Related Peptide
/ pharmacology
Colitis
/ chemically induced
Colon
/ blood supply
Cytokines
/ metabolism
Dextran Sulfate
Disease Models, Animal
Down-Regulation
/ drug effects
Granulocyte-Macrophage Progenitor Cells
/ metabolism
HLA-B27 Antigen
Leukapheresis
/ methods
Male
Rats
Rats, Inbred Lew
Rats, Transgenic
Receptor Activity-Modifying Protein 1
/ metabolism
Tumor Necrosis Factor-alpha
/ metabolism
Up-Regulation
/ drug effects
CGRP
colitis
leukocyte apheresis
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
11 04 2020
11 04 2020
Historique:
received:
26
06
2019
pubmed:
11
12
2019
medline:
9
7
2021
entrez:
11
12
2019
Statut:
ppublish
Résumé
The aim of this study was to address whether the therapeutic effect of leukocytapheresis (LCAP) depends on calcitonin gene- related peptide (CGRP) induction. An HLA-B27 transgenic rat model was treated with an LCAP column. The effects of LCAP on clinical, endoscopic, and histologic disease activity, the colony-forming ability of colony-forming unit (CFU)-granulocyte macrophages (GMs), colonic blood flow, and tissue expression of tumor necrosis factor (TNF)-α and CGRP were examined. Changes in the effects of LCAP after pretreatment with the CGRP antagonist CGRP8-37 were also observed. A dextran sulfate sodium-induced colitis rat model included treatment with CGRP, and the effect was assessed based on clinical, endoscopic, and histologic disease activity, colonic blood flow, the colony-forming ability of CFU-GMs, and tissue expression of inflammatory cytokines and CGRP receptor families. LCAP improved disease activity, enhanced colonic blood flow, and induced the bone marrow colony-forming ability of CFU-GMs with an increase in CGRP mRNA levels. These effects were abolished by pretreatment with CGRP8-37. The administration of CGRP suppressed colitis, promoting colonic blood flow, inducing bone marrow-derived cells, downregulating inflammatory cytokines, and upregulating receptor activity-modifying protein-1. The mRNA and protein levels of inflammatory cytokines in lipopolysaccharide-stimulated mononuclear cells were also decreased after CGRP treatment. The therapeutic effects of LCAP depend on CGRP induction. CGRP can effectively suppress colitis through the downregulation of inflammatory events and upregulation of protective events.
Sections du résumé
BACKGROUND
The aim of this study was to address whether the therapeutic effect of leukocytapheresis (LCAP) depends on calcitonin gene- related peptide (CGRP) induction.
METHODS
An HLA-B27 transgenic rat model was treated with an LCAP column. The effects of LCAP on clinical, endoscopic, and histologic disease activity, the colony-forming ability of colony-forming unit (CFU)-granulocyte macrophages (GMs), colonic blood flow, and tissue expression of tumor necrosis factor (TNF)-α and CGRP were examined. Changes in the effects of LCAP after pretreatment with the CGRP antagonist CGRP8-37 were also observed. A dextran sulfate sodium-induced colitis rat model included treatment with CGRP, and the effect was assessed based on clinical, endoscopic, and histologic disease activity, colonic blood flow, the colony-forming ability of CFU-GMs, and tissue expression of inflammatory cytokines and CGRP receptor families.
RESULTS
LCAP improved disease activity, enhanced colonic blood flow, and induced the bone marrow colony-forming ability of CFU-GMs with an increase in CGRP mRNA levels. These effects were abolished by pretreatment with CGRP8-37. The administration of CGRP suppressed colitis, promoting colonic blood flow, inducing bone marrow-derived cells, downregulating inflammatory cytokines, and upregulating receptor activity-modifying protein-1. The mRNA and protein levels of inflammatory cytokines in lipopolysaccharide-stimulated mononuclear cells were also decreased after CGRP treatment.
CONCLUSIONS
The therapeutic effects of LCAP depend on CGRP induction. CGRP can effectively suppress colitis through the downregulation of inflammatory events and upregulation of protective events.
Identifiants
pubmed: 31821463
pii: 5671688
doi: 10.1093/ibd/izz303
doi:
Substances chimiques
Cytokines
0
HLA-B27 Antigen
0
Ramp1 protein, rat
0
Receptor Activity-Modifying Protein 1
0
Tumor Necrosis Factor-alpha
0
Dextran Sulfate
9042-14-2
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
709-719Informations de copyright
© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.