Lipopolysaccharide and TNF-alpha modify adenosine A(2A) receptor expression and function in equine monocytes.
Abstract: Stimulation of adenosine A(2A) receptors results in anti-inflammatory effects in a variety of cell types. Lipopolysaccharide (LPS) and pro-inflammatory cytokines, such as TNF-alpha and IL-1, have been reported to up-regulate the expression of adenosine A(2A) receptors and thereby enhance the functional activity of adenosine A(2A) receptors in human and murine monocyte/macrophage cell lines and in monocytes/macrophages isolated from those species. In this study, we investigated the effects of LPS and TNF-alpha on the expression and functional activity of adenosine A(2A) receptors in isolated equine peripheral blood monocytes. The results of this study indicate that LPS and TNF-alpha up-regulate the transcription of adenosine A(2A) receptors for up to 24h; the response to LPS was of greater magnitude than the response to TNF-alpha. In this study, incubation with LPS, but not with TNF-alpha, resulted in down-regulation of adenosine A(3) receptor mRNA expression. Furthermore, incubation of these cells with LPS significantly increases the surface density of adenosine A(2A) receptors, and incubation with low concentrations of either LPS or TNF-alpha significantly increases the potency of the adenosine A(2A) receptor agonist, ATL313, to inhibit LPS-induced production of TNF-alpha. These findings suggest that the increased expression of adenosine A(2A) receptors and the enhanced functional potency of adenosine A(2A) receptor agonists after exposure to pro-inflammatory substances such as LPS or TNF-alpha may render adenosine A(2A) receptor agonists particularly important in the treatment of the systemic inflammatory response syndrome that occurs secondary to endotoxemia and bacterial infections in adult horses and neonatal foals.
Copyright 2009 Elsevier B.V. All rights reserved.
Publication Date: 2009-12-11 PubMed ID: 20056284DOI: 10.1016/j.vetimm.2009.12.001Google Scholar: Lookup
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- Journal Article
Summary
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This research investigates how substances Lipopolysaccharide (LPS) and TNF-alpha can affect the expression and activity of anti-inflammatory adenosine A(2A) receptors in equine monocytes, with implications for treating systemic inflammatory response syndrome in horses.
Research Objectives and Background
- The study’s purpose was to explore the impact of Lipopolysaccharide (LPS) and pro-inflammatory cytokine TNF-alpha on the expression and functional activity of adenosine A(2A) receptors in isolated equine monocytes.
- Interaction with adenosine A(2A) receptors is known to result in anti-inflammatory effects in different types of cells.
- LPS and cytokines such as TNF-alpha and IL-1 are known to increase the expression, and subsequently the activity, of adenosine A(2A) receptors in human and murine monocytes and macrophages.
Research Findings
- The study found that both LPS and TNF-alpha increase the transcription process of adenosine A(2A) receptors for a period of up to 24 hours. However, the response triggered by LPS was much stronger compared to TNF-alpha.
- When the monocytes were treated with LPS, but not TNF-alpha, there was a reduction in the expression of the adenosine A(3) receptor mRNA.
- LPS treatment significantly amplified the surface density of adenosine A(2A) receptors.
- Treatment with low concentrations of either LPS or TNF-alpha greatly improved the effectiveness of the adenosine A(2A) receptor agonist, ATL313, to inhibit the production of TNF-alpha resulting from LPS exposure.
Implication of the Research
- The research points to the potential therapeutic importance of adenosine A(2A) receptor agonists in treating the systemic inflammatory response syndrome (SIRS), specifically in cases caused by endotoxemia and bacterial infections in adult horses and neonatal foals.
- This syndrome arises secondary to these conditions, and the heightened expression of adenosine A(2A) receptors, as well as the increased potency of adenosine A(2A) receptor agonists after exposure to LPS or TNF-alpha, can be particularly crucial in its treatment.
Cite This Article
APA
Sun WC, Berghaus LJ, Moore JN, Hurley DJ, Vandenplas ML, Thompson R, Linden J.
(2009).
Lipopolysaccharide and TNF-alpha modify adenosine A(2A) receptor expression and function in equine monocytes.
Vet Immunol Immunopathol, 135(3-4), 289-295.
https://doi.org/10.1016/j.vetimm.2009.12.001 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
MeSH Terms
- Adenosine A2 Receptor Agonists
- Animals
- Animals, Newborn
- Base Sequence
- DNA Primers / genetics
- Horse Diseases / drug therapy
- Horse Diseases / metabolism
- Horses / genetics
- Horses / metabolism
- Humans
- In Vitro Techniques
- Lipopolysaccharides / pharmacology
- Mice
- Monocytes / drug effects
- Monocytes / metabolism
- Piperidines / pharmacology
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Radioligand Assay
- Receptor, Adenosine A2A / genetics
- Receptor, Adenosine A2A / metabolism
- Recombinant Proteins / pharmacology
- Systemic Inflammatory Response Syndrome / drug therapy
- Systemic Inflammatory Response Syndrome / metabolism
- Systemic Inflammatory Response Syndrome / veterinary
- Triazines / metabolism
- Triazoles / metabolism
- Tumor Necrosis Factor-alpha / pharmacology
Citations
This article has been cited 6 times.- Sohn R, Junker M, Meurer A, Zaucke F, Straub RH, Jenei-Lanzl Z. Anti-Inflammatory Effects of Endogenously Released Adenosine in Synovial Cells of Osteoarthritis and Rheumatoid Arthritis Patients. Int J Mol Sci 2021 Aug 19;22(16).
- Chen Y, Yu X, He Y, Zhang L, Huang X, Xu X, Chen M, Chen X, Wang L. Activation of A(2a)R attenuates bleomycin-induced pulmonary fibrosis via the SDF-1/CXCR4 axis-related pathway. Am J Transl Res 2017;9(9):4125-4136.
- Cronstein BN, Sitkovsky M. Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol 2017 Jan;13(1):41-51.
- Spooner R, DeGuzman J, Lee KL, Yilmaz O. Danger signal adenosine via adenosine 2a receptor stimulates growth of Porphyromonas gingivalis in primary gingival epithelial cells. Mol Oral Microbiol 2014 Apr;29(2):67-78.
- Lee CF, Lai HL, Lee YC, Chien CL, Chern Y. The A2A adenosine receptor is a dual coding gene: a novel mechanism of gene usage and signal transduction. J Biol Chem 2014 Jan 17;289(3):1257-70.
- Weisman GA, Ajit D, Garrad R, Peterson TS, Woods LT, Thebeau C, Camden JM, Erb L. Neuroprotective roles of the P2Y(2) receptor. Purinergic Signal 2012 Sep;8(3):559-78.
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