Cytokines upregulate vascular endothelial growth factor secretion by human airway smooth muscle cells: Role of endogenous prostanoids.
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.
Stocks
Joanne
J
Division of Respiratory Medicine, Clinical Sciences Building, City Hospital, Nottingham, UK.
Bradbury
Dawn
D
Corbett
Lisa
L
Pang
Linhua
L
Knox
Alan J
AJ
D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D003609:Dactinomycin; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin