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Adenosine Receptors and Inflammation

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Adenosine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 193))

Abstract

Extracellular adenosine is produced in a coordinated manner from cells following cellular challenge or tissue injury. Once produced, it serves as an autocrine- and paracrine-signaling molecule through its interactions with seven-membrane-spanning G-protein-coupled adenosine receptors. These signaling pathways have widespread physiological and pathophysiological functions. Immune cells express adenosine receptors and respond to adenosine or adenosine agonists in diverse manners. Extensive in vitro and in vivo studies have identified potent anti-inflammatory functions for all of the adenosine receptors on many different inflammatory cells and in various inflammatory disease processes. In addition, specific proinflammatory functions have also been ascribed to adenosine receptor activation. The potent effects of adenosine signaling on the regulation of inflammation suggest that targeting specific adenosine receptor activation or inactivation using selective agonists and antagonists could have important therapeutic implications in numerous diseases. This review is designed to summarize the current status of adenosine receptor signaling in various inflammatory cells and in models of inflammation, with an emphasis on the advancement of adenosine-based therapeutics to treat inflammatory disorders.

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Abbreviations

A1AR:

Adenosine A1 receptor

A2AAR:

Adenosine A2A receptor

A2BAR:

Adenosine A2B receptor

A3AR:

Adenosine A3 receptor

AC:

Adenylate cyclase

ADA:

Adenosine deaminase

AR:

Adenosine receptor

CD26:

Dipeptidyl pepsidase

CD39:

Ectonucleoside triphosphate diphosphohydrolase

CD73:

Ecto-5′-nucleotidase

CLP:

Cecal ligation and puncture

CNTs:

Concentrative nucleoside transporters

COPD:

Chronic obstructive pulmonary disease

DC:

Dendritic cell

ERK:

Extracellular signal-related protein kinase

fMLP:

Formyl methionyl-leucyl-phenylalanine

GRK:

G-protein-coupled receptor kinase

HIF:

Hypoxia-inducible factor

HMVECs:

Human microvascular endothelial cells

HPAECs:

Human pulmonary artery endothelial cells

HSP:

Heat shock protein

HUVEC:

Human umbilical vein endothelial cell

ICAM-1:

Intracellular adhesion molecule-1

IFN:

Interferon

IL:

Interleukin

imDC:

Immature dendritic cell

KO:

Knockout

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MHC:

Major histocompatibility complex

MIP:

Macrophage inflammatory protein

NF-κB:

Nuclear factor kappa B

NK:

Natural killer

NR:

Normothermic recirculation

PAF:

Platelet-activating factor

PBMCs:

Peripheral blood mononuclear cells

PDCs:

Plasmacytoid dendritic cells

PI3K:

Phosphoinositide 3-kinase

PKC:

Protein kinase C

PLC:

Phospholipase C

PTX:

Pertussis toxin

TCR:

T-cell receptor

TNF-α:

Tumor necrosis factor alpha

Tregs:

Regulatory T cells

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The University of Texas–Houston Medical School, 6431 Fannin, Houston, TX, 77030, USA

    Michael R. Blackburn & Eva Morschl

  2. Endacea, Inc., 2 Davis Drive, P.O Box 12076, Research Triangle Park, NC, 27709-2076, USA

    Constance O. Vance & Constance N. Wilson

Authors
  1. Michael R. Blackburn
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  2. Constance O. Vance
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  3. Eva Morschl
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  4. Constance N. Wilson
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Correspondence to Michael R. Blackburn .

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Editors and Affiliations

  1. Endacea, Inc.,, Davis Drive 2, Research Triangle Park, 27709-2076, U.S.A.

    Constance N. Wilson

  2. Health Sciences Center, West Virginia University, Health Sciences S. 2267, Morgantown, 26506-9104, U.S.A.

    S. Jamal Mustafa

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Blackburn, M.R., Vance, C.O., Morschl, E., Wilson, C.N. (2009). Adenosine Receptors and Inflammation. In: Wilson, C., Mustafa, S. (eds) Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89615-9_8

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