IL‐20 activates signaling pathways in endothelial cells and promotes angiogenic processes

Abstract

IL-20 transgenic mice develop hyperkeratosis, thickened epidermis, and proliferation in the suprabasal layer. Since expression of IL-20 is high in keratinocytes in suprapapillary foci in the psoriatic lesions, but low in uninvolved psoriatic skin, IL-20 might be implicated in psoriasis. The fact that angiogenesis and hypervascularity are characteristic features of the psoriatic plaque prompted us to investigate whether IL-20 has a potential role in the angiogenic process. We employed pig aorta endothelial (PAE) cells and found mRNA for both IL-20Rα- and β as well as IL-22R mRNA. Cell signaling studies revealed that the JAK/STAT pathway becomes activated (STAT5 and JAK2 phosphorylation) after IL-20 stimulation (5 nM) and furthermore that IL-20 activates the MAPkinase pathway (Erk1/2 phosphorylation) and the PI3K/Akt pathway. When the cells were plated on growth factor reduced matrigel they displayed tube formation in the presence of IL-20. However IL-20 had no effect on the rate of cell migration in a Boyden chamber assay (chemotaxia using 2% FCS) alone or in combination with VEGF (10 ng/ml) but migrating cells showed morphological changes and became elongated. In conclusion, endothelial cells are equipped with IL-20 receptors and IL-20 activates cell signaling that support angiogenic processes and causes endothelial tube formation. These findings combined with the observation that IL-20 promotes neovascularization in the mouse cornea assay (Cao et al, unpublished)suggests that IL-20 play a role in angiogenic processes in vivo.