Figure 3.

Major signaling pathways triggered by kinin B1 receptor (B1R) agonists in the human keratinocyte and its cross-talk with endothelial cells, fibroblasts, neutrophils and macrophages. Stimulation of kinin B1R in the human keratinocyte results in phosphorylation (P) of JunB that translocates into the nucleus to bind AP-1 sites and activate interleukin-4 (IL-4) synthesis. Release of IL-4 and also vascular endothelial growth factor (VEGF) from keratinocytes induces angiogenesis on blood vessels that expose VEGF receptors (VEGFR2) and IL-4 receptors (IL-4R) on the surface of endothelial cells. In addition, fibroblasts produce fibroblast growth factor-2 (FGF-2) and neutrophils and macrophages release VEGF that enhances the angiogenic response. Cytokines generated in the inflammatory milieu (TNF-ɑ, IL-1β, IL-2) may up-regulate the kinin B1R expressed by keratinocytes, neutrophils, macrophages and endothelial cells.