Cytokines upregulate vascular endothelial growth factor secretion by human airway smooth muscle cells: Role of endogenous prostanoids

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‐1β) and transforming growth factor beta (TGFβ). IL‐1β and TGFβ induced cyclo‐oxygenase (COX)‐2 protein and increased prostaglandin E2 (PGE2). Both IL‐1β and TGFβ increased VEGF‐A165 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‐1β but not TGFβ mediated VEGF‐A production. Furthermore, the effect of the COX inhibitors was overcome by adding exogenous PGE2. In conclusion, IL‐1β increases VEGF‐A secretion by COX‐2 derived PGE2 production whereas TGFβ uses COX‐independent pathways.

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