Induction Of IL-17 On The Migration And Tube Formation Of Vascular Endothelial Cells And The Inhibitory Effect Of Alkannin

Objective: Psoriasis is a systemic and inflammatory disease with dysfunction of the immune system under the combined action of keratinocytes,dendritic cells,and T cells.The abnormal angiogenesis in the skin is one of its main pathological manifestations.Interleukin-17(IL-17),which is often highly expressed in the psoriatic skin,has been proved to regulate the pathogenesis of the disease.Vascular endothelial cells are the main cells involved in the angiogenesis process.Studies have shown that IL-17 can act on vascular endothelial cells to promote angiogenesis.Alkannin,also known as Shikonin,is a monomeric ingredient extracted from the root of comfrey.Comfrey was used for anti-inflammatory,hemostatic,and psoriasis treatments in history.This experiment used cell and animal experiments to investigate the effects of IL-17 on vascular endothelial cells and observe the effects of Alkannin on IL-17.Methods: Tube formation experiment: Human umbilical vein endothelial cells(HUVECs)were cultured and divided into control group(PBS)and model group(IL-17).Control group: PBS was added to the cell culture medium;Model group: IL-17(100ng / ml)was added to the cell culture medium.The effect of IL-17 on HUVECs' tube formation ability was observed after 5 hours;Matrigel plug assay in mice: 15 4-6 weeks old male C57 BL / 6 mice were randomly divided into 5 groups(n = 3): control group(CON),model group(IL-17),positive control group(MTX),Alkannin low-dose group(ALK-2.5)and Alkannin high-dose group(ALK-5).A mouse matrigel plug assay was used to simulate the subcutaneous environment,and each group was given a gavage once a day for 12 days.The control group and model group were given matrix oil(2.5% DMSO,200?l/d),and the positive control group was given Methotrexate(MTX,0.5mg/kg/d),Alkannin low-dose group was given Alkannin(Alkannin,2.5mg/kg/d),Alkannin high-dose group was given Alkannin(Alkannin,5mg/kg/d).On the 14 th day,mice were sacrificed,and the matrigel plugs were collected.The pathological phenomena were observed by HE staining,and the expression of vascular endothelial cell surface marker CD34 and vascular endothelial growth factor(VEGF)were observed by immunohistochemical staining.Results: Tube formation experiment: Compared with the control group,the tube formation ability of HUVEC in the model group was significantly enhanced;Matrigel plug assay in mice: Compared with the control group,the plugs of the model group had microvascular formation,the number of vascular endothelial cells in the plugs increased,and the expression of VEGF also increased.Compared with the model group,the number of microvessels and vascular endothelial cells,and the expression of VEGF were all decreased,which were more obvious in the high-dose group.Conclusion: 1.IL-17 can promote the tube formation of HUVECs cultured in vitro.2.IL-17 can induce the migration and tube formation of vascular endothelial cells in mice,and enhance the expression of VEGF.3.Alkannin can significantly inhibit the pro-angiogenic effect of IL-17.