Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells

Vascular endothelial growth factor (VEGF) is an endothelial permeability mediator that is highly expressed in lung epithelium. In nonlung cells proinflammatory cytokines have been shown to increase VEGF expression, but their effects on lung epithelium remain unclear. We hypothesized that increases i...

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Main Authors: James P. Maloney, Li Gao
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/387842
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author James P. Maloney
Li Gao
author_facet James P. Maloney
Li Gao
author_sort James P. Maloney
collection DOAJ
description Vascular endothelial growth factor (VEGF) is an endothelial permeability mediator that is highly expressed in lung epithelium. In nonlung cells proinflammatory cytokines have been shown to increase VEGF expression, but their effects on lung epithelium remain unclear. We hypothesized that increases in alveolar epithelial cell VEGF RNA and protein expression occur after exposure to proinflammatory cytokines. We tested this using human alveolar epithelial cells (A549) stimulated with 5 proinflammatory cytokines. VEGF RNA expression was increased 1.4–2.7-fold in response to IL-1, IL-6, IL-8, TNF-α, or TGF-β over 6 hours, with TGF-β having the largest response. TNF-α increased VEGF RNA as early as 1 hour. A mix of IL-1, IL-6, and IL-8 had effects similar to IL-1. TNF-α increased protein expression as early as 4 hours and had a sustained effect at 16 hours, whereas IL-1 did not increase protein expression. Only VEGF165 was present in cultured A549 cells, yet other isoforms were seen in human lung tissue. Increased expression of VEGF in alveolar epithelial cells occurs in response to proinflammatory cytokines. Increased VEGF expression likely contributes to the pathogenesis of inflammatory lung diseases and to the angiogenic phenotype of lung cancer, a disease typically preceded by chronic inflammation.
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spelling doaj-art-b47a2ebf453545d0b55771b91cc8e23e2025-02-03T00:59:31ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/387842387842Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial CellsJames P. Maloney0Li Gao1Division of Pulmonary and Critical Care Medicine, University of Colorado Denver, 12700 East 19th Avenue, C272, Aurora, CO 80045, USADivision of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Room 3A.62A, 5501 Hopkins Bayview Circle, Baltimore, MD 21224-6801, USAVascular endothelial growth factor (VEGF) is an endothelial permeability mediator that is highly expressed in lung epithelium. In nonlung cells proinflammatory cytokines have been shown to increase VEGF expression, but their effects on lung epithelium remain unclear. We hypothesized that increases in alveolar epithelial cell VEGF RNA and protein expression occur after exposure to proinflammatory cytokines. We tested this using human alveolar epithelial cells (A549) stimulated with 5 proinflammatory cytokines. VEGF RNA expression was increased 1.4–2.7-fold in response to IL-1, IL-6, IL-8, TNF-α, or TGF-β over 6 hours, with TGF-β having the largest response. TNF-α increased VEGF RNA as early as 1 hour. A mix of IL-1, IL-6, and IL-8 had effects similar to IL-1. TNF-α increased protein expression as early as 4 hours and had a sustained effect at 16 hours, whereas IL-1 did not increase protein expression. Only VEGF165 was present in cultured A549 cells, yet other isoforms were seen in human lung tissue. Increased expression of VEGF in alveolar epithelial cells occurs in response to proinflammatory cytokines. Increased VEGF expression likely contributes to the pathogenesis of inflammatory lung diseases and to the angiogenic phenotype of lung cancer, a disease typically preceded by chronic inflammation.http://dx.doi.org/10.1155/2015/387842
spellingShingle James P. Maloney
Li Gao
Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells
Mediators of Inflammation
title Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells
title_full Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells
title_fullStr Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells
title_full_unstemmed Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells
title_short Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells
title_sort proinflammatory cytokines increase vascular endothelial growth factor expression in alveolar epithelial cells
url http://dx.doi.org/10.1155/2015/387842
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