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Glial A Adenosine Receptors Modulate Abnormal Tachykininergic Responses and Prevent Enteric Inflammation Associated with High Fat Diet-Induced Obesity.
D'Antongiovanni, Vanessa Benvenuti, Laura Fornai, Matteo Pellegrini, Carolina van den Wijngaard, Renè Cerantola, Silvia Giron, Maria Cecilia Caputi, Valentina Colucci, Rocchina Haskó, Gyorgy
D'Antongiovanni, Vanessa
Benvenuti, Laura
Fornai, Matteo
Pellegrini, Carolina
van den Wijngaard, Renè
Cerantola, Silvia
Giron, Maria Cecilia
Caputi, Valentina
Colucci, Rocchina
Haskó, Gyorgy
Advisors
Editors
Other Contributors
Departments
Date
18/05/2020
Date Submitted
Keywords
adenosine A2B receptors
colonic motor dysfunction
enteric glia
enteric inflammation
glial cell derived neurotrophic factor
interleukin-1β
OBESITY
substance P
tachykininergic contraction
toll-like receptor 4
colonic motor dysfunction
enteric glia
enteric inflammation
glial cell derived neurotrophic factor
interleukin-1β
OBESITY
substance P
tachykininergic contraction
toll-like receptor 4
Other Subjects
Subject Mesh
Planned Date
Start Date
Collaborators
Principal Investigators
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cells-09-01245-v2.pdf
Adobe PDF, 3.06 MB
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Abstract
The role played by adenosine A2B receptors (A2BRs) in the regulation of enteric glial cell (EGC) functions remains unclear. This study was aimed at investigating the involvement of A2BRs in the control of EGC functions in a model of obesity. C57BL/6 mice were fed with standard diet (SD) or high fat diet (HFD) for eight weeks. Colonic tachykininergic contractions were recorded in the presence of BAY60-6583 (A2BRs agonist), MRS1754 (A2BRs antagonist), and the gliotoxin fluorocitrate. Immunofluorescence distribution of HuC/D, S100β, and A2BRs was assessed in whole mount preparations of colonic myenteric plexus. To mimic HFD, EGCs were incubated in vitro with palmitate (PA) and lipopolysaccharide (LPS), in the absence or in the presence of A2BR ligands. Toll-like receptor 4 (TLR4) expression was assessed by Western blot analysis. Interleukin-1β (IL-1β), substance P (SP), and glial cell derived neurotrophic factor (GDNF) release were determined by enzyme-linked immunosorbent assay (ELISA) assays. MRS1754 enhanced electrically evoked tachykininergic contractions of colonic preparations from HFD mice. BAY60-6583 decreased the evoked tachykininergic contractions, with higher efficacy in HFD mice. Such effects were blunted upon incubation with fluorocitrate. In in vitro experiments on EGCs, PA and LPS increased TLR4 expression as well as IL-1β, GDNF, and SP release. Incubation with BAY60-6583 reduced TLR4 expression as well as IL-1β, GDNF, and SP release. Such effects were blunted by MRS1754. The present results suggest that A2BRs, expressed on EGCs, participate in the modulation of enteric inflammation and altered tachykininergic responses associated with obesity, thus representing a potential therapeutic target.
Language
en
Citation
ISSN
eISSN
2073-4409
ISBN
DOI
10.3390/cells9051245
PMID
32443525