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-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.