Affiliation:
1. Department of Dermatology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an China
2. Center for Translational Medicine The First Affiliated Hospital of Xi'an Jiaotong University Xi'an China
3. Department of Clinical Laboratory The First Affiliated Hospital of Xi'an Jiaotong University Xi'an China
4. Institute of Molecular and Translational Medicine, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an China
5. Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University) Ministry of Education Xi'an China
Abstract
AbstractBackgroundElevated IL‐21 expression which can effectively induce Th17 cell differentiation has been implicated in the pathogenesis of psoriasis, but its role in angiogenesis remains poorly understood.MethodsPASI and PSI score assessment was applied to evaluate the severity of psoriatic lesions. The expression of IL‐21, IL‐21 receptor (IL‐21R), CD31, VEGFA, MMP‐9, and ICAM‐1 in skin was determined by immunohistochemistry or quantitative real‐time polymerase chain reaction. The serum level of IL‐21 was measured by enzyme‐linked immunosorbent assay (ELISA). Then, their correlation was analyzed statistically. Human umbilical vein endothelial cells (HUVECs) cocultured with conditional medium from normal human epidermal keratinocytes (NHEKs) were treated with IL‐21 and/or M5 cocktail (mixture of IL‐1α, IL‐17A, IL‐22, TNF‐α, and oncostatin M). The migration and tube formation of HUVECs were detected, and the levels of VEGFA, MMP‐9, and ICAM‐1 in NHEKs were measured by Western blotting or ELISA.ResultsIncreased IL‐21 and IL‐21R expression was observed in psoriatic sera or skin specimens, with IL‐21R mainly locating in keratinocytes and IL‐21 in immune cells. Pearson analysis showed significantly positive correlation between IL‐21/IL‐21R and erythema scores/microvessel density in psoriatic lesions. Moreover, the expression of proangiogenic genes, VEGFA, ICAM‐1, and MMP‐9 was upregulated in skins of psoriasis. Additionally, in M5 microenvironment, migration and tube formation could be magnified in HUVECs using IL‐21 pre‐treated NHEK medium. Mechanically, the co‐stimulation of IL‐21 and M5 to NEHKs increased the expression of ICAM‐1.ConclusionIL‐21 could regulate keratinocytes to secrete ICAM‐1, thereby promoting angiogenesis in psoriasis.
Funder
Key Research and Development Projects of Shaanxi Province
National Natural Science Foundation of China
Xi’an Jiaotong University
Subject
Genetics,Molecular Biology,Biochemistry,Biotechnology