Proinflammatory cytokines upregulate mRNA expression and secretion of vascular endothelial growth factor in cultured human airway smooth muscle cells |
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Authors: | V K T Alagappan S McKay A Widyastuti I M Garrelds A J J C Bogers H C Hoogsteden S J Hirst H S Sharma |
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Institution: | (1) Department of Pharmacology, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherland;(2) Department of Cardiothoracic Surgery, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherland;(3) Department of Pulmonary Medicine Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherland;(4) Asthma, Allergy & Respiratory Science, The Guy's, King's College & St. Thomas' School of Medicine, King's College London, London, UK |
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Abstract: | Airflow obstruction in chronic airway disease is associated with airway and pulmonary vascular remodeling, of which the molecular
mechanisms are poorly understood. Paracrine actions of angiogenic factors released by resident or infiltrating inflammatory
cells following activation by proinflammatory cytokines in diseased airways could play a major role in the airway vascular
remodeling process. Here, the proinflammatory cytokines interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were investigated
on cell cultures of human airway smooth muscle (ASM) for their effects on mRNA induction and protein release of the angiogenic
peptide, vascular endothelial growth factor (VEGF). IL-1β (0.5 ng/mL) and TNF-α (10ng/mL) each increased VEGF mRNA (3.9 and
1.7 kb) expression in human ASM cells, reaching maximal levels between 16 and 24 and 4 and 8h, respectively. Both cytokines
also induced a time-dependent release of VEGF, which was not associated with increased ASM growth. Preincubation of cells
with 1μM dexamethasone abolished enhanced release of VEGF by TNF-α. The data suggest that human ASM cells express and secrete
VEGF in response to proinflammatory cytokines and may participate in paracrine inflammatory mechanisms of vascular remodeling
in chronic airway disease. |
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Keywords: | Cytokine vascular endothelial growth factor airway smooth muscle enzymelinked immunosorbent assay human |
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