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Differential modulation of lipopolysaccharide-induced expression of inflammatory genes in equine monocytes through activation of adenosine A2A receptors.
- Source :
-
Veterinary immunology and immunopathology [Vet Immunol Immunopathol] 2010 Apr 15; Vol. 134 (3-4), pp. 169-77. Date of Electronic Publication: 2009 Sep 02. - Publication Year :
- 2010
-
Abstract
- Adenosine is an endogenous nucleoside that has potent receptor-mediated immunomodulatory effects on macrophage/monocyte function. In this study, we determined the effects of an adenosine A(2A) receptor agonist, ATL313, on the expression of mRNAs for four pro-inflammatory mediators, IL-1beta, IL-8, COX-2, and TNF-alpha, and the mRNA and protein for the anti-inflammatory cytokine, IL-10 in equine monocytes incubated with lipopolysaccharide (LPS). The results indicate that ATL313 significantly reduces LPS-induced expression of COX-2 and TNF-alpha, enhances the expression of IL-10 and IL-8, but does not alter the expression of IL-1beta. These effects of ATL313 were reversed by co-incubation with the selective adenosine A(2A) antagonist ZM241385, and were mimicked by the cAMP analogue dibutyryl cAMP. These differential effects of adenosine A(2A) receptor activation were in contrast to those obtained using the P38 MAPK inhibitor, SB203580, which nearly abolished all LPS-induced changes in mRNA expression as well as the production of TNF-alpha protein. These findings, which indicate that adenosine A(2A) receptor activation modulates the transcription of several, but not all, pro-inflammatory mediators and exerts a synergistic effect on the induction of at least one anti-inflammatory cytokine, suggest that selective adenosine A(2A) agonists may reduce the early pro-inflammatory effects of endotoxemia in horses.<br /> (Copyright 2009 Elsevier B.V. All rights reserved.)
- Subjects :
- Adenosine A2 Receptor Agonists
Animals
Base Sequence
Bucladesine pharmacology
Cyclooxygenase 2 genetics
Cytokines genetics
Cytokines metabolism
DNA Primers genetics
Drug Synergism
Gene Expression drug effects
Horses metabolism
Imidazoles pharmacology
In Vitro Techniques
Interleukin-10 biosynthesis
Lipopolysaccharides administration & dosage
Lipopolysaccharides toxicity
Monocytes drug effects
Monocytes immunology
Monocytes metabolism
Piperidines administration & dosage
Piperidines pharmacology
Pyridines pharmacology
Horses genetics
Horses immunology
Inflammation Mediators metabolism
Receptor, Adenosine A2A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2534
- Volume :
- 134
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Veterinary immunology and immunopathology
- Publication Type :
- Academic Journal
- Accession number :
- 19766323
- Full Text :
- https://doi.org/10.1016/j.vetimm.2009.08.018