Abstract
Here, we report that vascular endothelial growth factor (VEGF)-A secretion by human airway smooth muscle cells was increased by interleukin 1 beta (IL-1beta) and transforming growth factor beta (TGFbeta). IL-1beta and TGFbeta induced cyclo-oxygenase (COX)-2 protein and increased prostaglandin E(2) (PGE(2)). Both IL-1beta and TGFbeta increased VEGF-A(165) mRNA and VEGF promoter luciferase construct activity, in addition VEGF-A protein was inhibited by actinomycin D suggesting transcriptional regulation. The COX inhibitors indomethacin and NS398 inhibited IL-1beta but not TGFbeta mediated VEGF-A production. Furthermore, the effect of the COX inhibitors was overcome by adding exogenous PGE(2). In conclusion, IL-1beta increases VEGF-A secretion by COX-2 derived PGE(2) production whereas TGFbeta uses COX-independent pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Survival / drug effects
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Cells, Cultured
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Cytokines / antagonists & inhibitors*
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Cytokines / pharmacology
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Dactinomycin / pharmacology
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Dinoprostone / biosynthesis*
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Dose-Response Relationship, Drug
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Enzyme Induction
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Humans
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Indomethacin / pharmacology
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Interleukin-1 / antagonists & inhibitors
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Interleukin-1 / pharmacology
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Kinetics
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Luciferases / metabolism
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Membrane Proteins
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Muscle, Smooth / cytology
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Muscle, Smooth / drug effects*
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Muscle, Smooth / enzymology
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Nitrobenzenes / pharmacology
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Prostaglandin-Endoperoxide Synthases / biosynthesis*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Sulfonamides / pharmacology
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Trachea / cytology
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Trachea / drug effects*
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Trachea / enzymology
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Transforming Growth Factor beta / pharmacology
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Up-Regulation / drug effects*
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Vascular Endothelial Growth Factor A / metabolism*
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Cytokines
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Interleukin-1
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Membrane Proteins
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Nitrobenzenes
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RNA, Messenger
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Sulfonamides
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Transforming Growth Factor beta
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Vascular Endothelial Growth Factor A
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Dactinomycin
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Luciferases
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone
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Indomethacin