Shikonin suppresses IL-17-induced VEGF expression via blockage of JAK2/STAT3 pathway

• Shikonin decreased IL-17-induced VEGF expression in vivo and in vitro.
• Shikonin exerts a suppressive effect on IL-17-induced JAK2/STAT3 signaling.
• Shikonin decreased IL-17-induced VEGF expression by the inhibition of JAK2/STAT3 signaling.

IL-17 signaling in keratinocytes plays an important role in psoriasis, which is a benign, chronic skin disease characterized by keratinocytes hyperproliferation and increased dermal vascularity. Shikonin, isolated from the traditional medical herbs Lithospermum erythrorhizon, has long been found to possess different medicinal properties such as antibacterial, improving wound healing, anti-inflammatory and anti-tumor effects. However, the effects and mechanisms of shikonin on VEGF expression in keratinocytes mediated by IL-17 signaling, are still not fully clarified. In the present study, we investigated the effects and regulatory mechanisms of shikonin on VEGF expression in keratinocytes induced by IL-17 by in vitro and in vivo experiments. Our results showed that shikonin significantly inhibited IL-17-induced VEGF mRNA and protein expression in HaCaT cells and the secretion of VEGF by HaCaT cells, inhibited IL-17-induced IL-17R, pJAK2 and pSTAT3 expression, while up-regulated the expression of SOCS1 in HaCaT cells. Additionally, shikonin effectively suppressed VEGF expression in the skin of IL-17 stimulated mice. Furthermore, shikonin suppressed VEGF-induced tube formation of HUVECs and CD34 expression in the skin of IL-17 stimulated mice. These results imply that shikonin suppresses IL-17-induced VEGF expression in vitro and in vivo and the mechanisms may be related to its effect in blockage of JAK2/STAT3 pathway. These data deepen our understanding of shikonin in the inhibition of angiogenesis in inflammatory skin diseases such as psoriasis.