STIMULATION OF ADENOSINE A2A RECEPTOR INHIBITS LPS-INDUCED EXPRESSION OF INTERCELLULAR ADHESION MOLECULE 1 AND PRODUCTION OF TNF-α IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS

Hamano, Ryosuke; Takahashi, Hideo; Ishibashi, Hiromi; Kanke, Toru; Liu, Keyue; Yoshino, Tadashi; Sendo, Toshiaki; Nishibori, Masahiro; Tanaka, Noriaki

doi:10.1097/shk.0b013e31812385da

Cited by 18 publications

(23 citation statements)

References 17 publications

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“…Nicotine dose dependently reduced TNF production in 4 out of 11 human whole blood samples, whereas in one sample TNF release was enhanced. Other studies report that in other cell types, such as peripheral blood-derived human macrophages [1] and mononuclear cells [36], nicotinic receptor activation reduced TNF production in all samples. On the other hand, Kox et al [37] reported that nicotine attenuated TNF release equally on PBMCs, monocytes and human whole blood samples, but only at a high dosage of 1 m M .…”

Section: Discussionmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor Expression and Susceptibility to Cholinergic Immunomodulation in Human Monocytes of Smoking Individuals

Zanden

Hilbers²,

Verseijden³

et al. 2012

Neuroimmunomodulation

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Objective: Smoking is generally accepted as a factor that affects the disease course in inflammatory bowel disease patients. Whether these effects can be contributed to the immunomodulatory effects of nicotine via nicotinic acetylcholine receptor (nAChR) activation is unclear. As previous data suggest that the α7 nicotinic acetylcholine receptor (CHRNA7) and its duplicated variant CHRFAM7A may specifically participate in the inflammatory response of monocytes, we evaluated whether repeated nicotine exposure or smoking affects monocyte CHRNA7 and CHRFAM7A expression and cholinergic immunomodulation. Methods: The human monocyte cell line THP-I was incubated with nicotine for different time points before endotoxin exposure. In a pilot volunteer study using smoking (n = 4) and nonsmoking (n = 7) individuals, vagal output was stimulated by olive oil administration after which monocytes were analyzed for nicotinic receptor expression. Serum tumor necrosis factor (TNF) levels were determined using ELISA and expression levels of the nAChR subunits CHRNA7, CHRNB2 or CHRFAM7A were analyzed using QPCR. Results: Repeated nicotine exposure upregulated CHRNA7 expression on THP-I monocytes and led to an enhanced potential of α7 nAChR agonist GSK1345038A to reduce TNF levels. Furthermore, CHRNA7 was only detectable in isolated blood monocytes of smokers. On the other hand, the expression of CHRFAM7A and CHRNB2 was not affected by nicotine exposure. Lipopolysaccharides-induced TNF secretion was inhibited by nicotinic receptor activation in THP-I monocytes, but this response was not consistently seen in blood monocytes from smoking individuals. Conclusions: We conclude that CHRNA7 expression on blood monocytes is upregulated in smoking individuals, which may contribute to cholinergic immunomodulation.

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Section: Discussionmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor Expression and Susceptibility to Cholinergic Immunomodulation in Human Monocytes of Smoking Individuals

Zanden

Hilbers²,

Verseijden³

et al. 2012

Neuroimmunomodulation

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“…ADORA2A is an important regulator of inflammation in other models of injury, yet the actions of ADORA2A in macrophages remain largely unknown (25,29,(45)(46)(47)(48). Because CGS-21680 does express weak affinity for another adenosine receptor, ADORA2B (1/100 potency compared with ADORA2A), we used NECA as a nonselective AR agonist to assess the potential additional contribution of ADORA2B to the observed response in our model (11).…”

Section: Discussionmentioning

confidence: 99%

Macrophage A2A Adenosinergic Receptor Modulates Oxygen-Induced Augmentation of Murine Lung Injury

Aggarwal¹,

D’Alessio²,

Eto³

et al. 2013

Am J Respir Cell Mol Biol

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Acute respiratory distress syndrome (ARDS) causes significant morbidity and mortality. Exacerbating factors increasing the risk of ARDS remain unknown. Supplemental oxygen is often necessary in both mild and severe lung disease. The potential effects of supplemental oxygen may include augmentation of lung inflammation by inhibiting antiinflammatory pathways in alveolar macrophages. We sought to determine oxygen-derived effects on the anti-inflammatory A2A adenosinergic (ADORA2A) receptor in macrophages, and the role of the ADORA2A receptor in lung injury. Wild-type (WT) and ADORA2A2/2 mice received intratracheal lipopolysaccharide (IT LPS), followed 12 hours later by continuous exposure to 21% oxygen (control mice) or 60% oxygen for 1 to 3 days. We measured the phenotypic endpoints of lung injury and the alveolar macrophage inflammatory state. We tested an ADORA2A-specific agonist, CGS-21680 hydrochloride, in LPS plus oxygen-exposed WT and ADORA2A 2/2 mice. We determined the specific effects of myeloid ADORA2A, using chimera experiments. Compared with WT mice, ADORA2A2/2 mice exposed to IT LPS and 60% oxygen demonstrated significantly more histologic lung injury, alveolar neutrophils, and protein. Macrophages from ADORA2A 2/2 mice exposed to LPS plus oxygen expressed higher concentrations of proinflammatory cytokines and cosignaling molecules. CGS-21680 prevented the oxygen-induced augmentation of lung injury after LPS only in WT mice. Chimera experiments demonstrated that the transfer of WT but not ADORA2A 2/2 bone marrow cells into irradiated ADORA2A2/2 mice reduced lung injury after LPS plus oxygen, demonstrating myeloid ADORA2A protection. ADORA2A is protective against lung injury after LPS and oxygen. Oxygen after LPS increases macrophage activation to augment lung injury by inhibiting the ADORA2A pathway.

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“…Adenosine inhibits LPS-induced production of TNF by murine peritoneal macrophages but increases that of IL-6 [21,27]. A2AR activation, with the selective adenosine congener 2- p -(2-Carboxyethyl)phenethylamino-5′- N -ethyl-carboxamidoadenosine (CGS-21680), inhibits LPS-induced TNF production in human peripheral blood mononuclear cells (PBMCs) [28], monocytes [29], human lung macrophages [30] and murine macrophages [31]. The AR agonist 5′- N -ethylcarboxamidoadenosine (NECA) activated A2AR and increased cAMP in human monocytes thereby inhibiting LPS-induced IL-12p70 while enhancing IL-10 production in human whole blood [23].…”

Section: Adenosine In Innate Immunitymentioning

confidence: 99%

Adenosine modulates Toll-like receptor function: basic mechanisms and translational opportunities

Coombs

Belderbos

Gallington

et al. 2011

Expert Review of Anti-infective Therapy

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Adenosine is an endogenous purine metabolite whose concentration in human blood plasma rises from nanomolar to micromolar during stress or hypoxia. Leukocytes express seven-transmembrane adenosine receptors whose engagement modulates Toll-like receptor-mediated cytokine responses, in part via modulation of intracellular cyclic adenosine monophosphate (cAMP). Adenosine congeners are used clinically to treat arrhythmias and apnea of prematurity. Herein we consider the potential of adenosine congeners as innate immune response modifiers to prevent and/or treat infection.

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STIMULATION OF ADENOSINE A2A RECEPTOR INHIBITS LPS-INDUCED EXPRESSION OF INTERCELLULAR ADHESION MOLECULE 1 AND PRODUCTION OF TNF-α IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS

Cited by 18 publications

References 17 publications

Nicotinic Acetylcholine Receptor Expression and Susceptibility to Cholinergic Immunomodulation in Human Monocytes of Smoking Individuals

Nicotinic Acetylcholine Receptor Expression and Susceptibility to Cholinergic Immunomodulation in Human Monocytes of Smoking Individuals

Macrophage A2A Adenosinergic Receptor Modulates Oxygen-Induced Augmentation of Murine Lung Injury

Adenosine modulates Toll-like receptor function: basic mechanisms and translational opportunities

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