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 E 2 (PGE 2 ). Both IL‐1β and TGFβ 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‐1β but not TGFβ mediated VEGF‐A production. Furthermore, the effect of the COX inhibitors was overcome by adding exogenous PGE 2 . In conclusion, IL‐1β increases VEGF‐A secretion by COX‐2 derived PGE 2 production whereas TGFβ uses COX‐independent pathways.