Acotiamide attenuates central urocortin 2-induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF-α productions in LPS-stimulated macrophage cell lines.
Animals
Benzamides
/ pharmacology
Cell Line
Gastrointestinal Agents
/ pharmacology
Inflammation
/ chemically induced
Interleukin-6
/ metabolism
Intestines
/ drug effects
Lipopolysaccharides
Macrophages
/ drug effects
Male
Phosphorylation
/ drug effects
Rats
Rats, Sprague-Dawley
Signal Transduction
/ drug effects
Thiazoles
/ pharmacology
Tumor Necrosis Factor-alpha
/ metabolism
Urocortins
TNF-α
functional dyspepsia
gastric emptying
intestinal inflammation
urocortin 2
Journal
Neurogastroenterology and motility
ISSN: 1365-2982
Titre abrégé: Neurogastroenterol Motil
Pays: England
ID NLM: 9432572
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
03
09
2019
revised:
21
12
2019
accepted:
09
01
2020
pubmed:
8
2
2020
medline:
27
7
2021
entrez:
8
2
2020
Statut:
ppublish
Résumé
To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS-stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model. Rats were divided into four groups. LPS-stimulated group (n = 4); LPS- and urocortin 2-treated group (n = 4); LPS- and acotiamide-treated group (n = 4); and LPS-, urocortin 2-, and acotiamide-treated group (n = 4). CD68-, CCR2-, and corticotropin-releasing hormone receptor type 2 (CRHR2)-positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF-α, IL-6, and IL-4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue. Central administration of Ucn 2 significantly aggravated infiltrations of CD68- and CCR2-positive cells in the intestinal mucosa of LPS-stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68- and CCR2-positive cells in the jejunum of central Ucn 2-treated LPS-stimulated rat models. Acotiamide significantly reduced the expression levels of IkB-α phosphorylation in LPS- and MCP-1-stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF-α and IL-6 productions in LPS-stimulated NR8383 cells and astressin B reversed the inhibition of TNF-α production in stimulated NR8383 cells. Acotiamide (30 μmol/L) significantly reduced TNF-α and IL-6 productions in LPS- and MCP-1-stimulated NR8383 cells. Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them.
Sections du résumé
BACKGROUND
To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS-stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model.
METHODS
Rats were divided into four groups. LPS-stimulated group (n = 4); LPS- and urocortin 2-treated group (n = 4); LPS- and acotiamide-treated group (n = 4); and LPS-, urocortin 2-, and acotiamide-treated group (n = 4). CD68-, CCR2-, and corticotropin-releasing hormone receptor type 2 (CRHR2)-positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF-α, IL-6, and IL-4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue.
KEY RESULTS
Central administration of Ucn 2 significantly aggravated infiltrations of CD68- and CCR2-positive cells in the intestinal mucosa of LPS-stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68- and CCR2-positive cells in the jejunum of central Ucn 2-treated LPS-stimulated rat models. Acotiamide significantly reduced the expression levels of IkB-α phosphorylation in LPS- and MCP-1-stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF-α and IL-6 productions in LPS-stimulated NR8383 cells and astressin B reversed the inhibition of TNF-α production in stimulated NR8383 cells. Acotiamide (30 μmol/L) significantly reduced TNF-α and IL-6 productions in LPS- and MCP-1-stimulated NR8383 cells.
CONCLUSIONS AND INFERENCES
Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them.
Substances chimiques
Benzamides
0
Gastrointestinal Agents
0
Interleukin-6
0
Lipopolysaccharides
0
Thiazoles
0
Tumor Necrosis Factor-alpha
0
Urocortins
0
Z 338
D42OWK5383
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13813Subventions
Organisme : The Ministry of Education, Culture, and Science and the Ministry of Health, Japan (16K09294)
ID : 16K09294
Pays : International
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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