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Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

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Author: Verhoeckx, K.C.M. · Doornbos, R.P. · Witkamp, R.F. · Greef, J. van der · Rodenburg, R.J.T.
Institution: TNO Kwaliteit van Leven
Source:International Immunopharmacology, 1, 6, 1-7
Identifier: 239053
doi: doi:10.1016/j.intimp.2005.05.013
Keywords: Biology · Analytical research · β2-adrenergic receptor · β2-adrenergic receptor agonist · cAMP · Clenbuterol · CXCL6 · GCP-2 · Oncostatin M · VEGF · Zilpaterol · 3 isopropylamino 1 (7 methyl 4 indanyloxy) 2 butanol · beta 2 adrenergic receptor · beta 2 adrenergic receptor blocking agent · beta 2 adrenergic receptor stimulating agent · bronchodilating agent · butyryl cyclic AMP · chemokine · chemokine cxcl 6 · clenbuterol · Escherichia coli lipopolysaccharide · forskolin · oncostatin M · prostaglandin E2 · unclassified drug · vasculotropin · zilpaterol · angiogenesis · article · asthma · controlled study · drug potency · histiocytic lymphoma · human · human cell · lymphoma cell · macrophage · neutrophil · priority journal · upregulation · Adrenergic beta-Agonists · Bucladesine · Chemokines, CXC · Clenbuterol · Cyclic AMP · Cytokines · Dinoprostone · Forskolin · Humans · Lipopolysaccharides · Macrophage Activation · Macrophages · Oncostatin M · Trimethylsilyl Compounds · U937 Cells · Up-Regulation · Vascular Endothelial Growth Factor A


Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (β2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents that induce intracellular cAMP (prostaglandin E2, forskolin, and butyryl cAMP). LPS in combination with β2- agonists and cAMP elevating agents had an additional effect on the release of VEGF, OSM, and CXCL6. These proteins are up-regulated after 16-24 h of exposure and this is mediated by the β2-AR, as determined by time course experiments and the use of a specific β2-AR antagonist (ICI 118551). Beta2-AR agonists are used as bronchodilators in the treatment of asthma, but appear to have no effect on the chronic inflammation of the disease. However, the up-regulation of VEGF, OSM, and CXCL6 may have adverse effects on the inflammatory process of asthma. These mediators are involved in the recruitment of neutrophils, airway remodelling and angiogenesis, known features of chronic inflammatory diseases. We propose that the up-regulation of these proteins could play a role in the adverse effects of prolonged excessive usage of β2-AR agonists on the airways besides the desensitization of the β2-AR. © 2005 Elsevier B.V. All rights reserved.