IL-21在银屑病小鼠皮损中的表达及作用机制

The Expression and Mechanism of IL-21 in Psoriasis Mouse Lesions

目的 了解白介素(interleukin, IL)-21在银屑病小鼠皮损中的表达特征及其在银屑病发病中的作用机制。方法 20只雄性BALB/c小鼠随机分为对照组、模型组、阿维A灌胃组、灭菌水灌胃组。5%咪喹莫特乳膏背部使用诱导小鼠银屑病模型,连续造模7 d后拍照计算各组小鼠PASI评分,取小鼠皮损观察组织病理学改变,利用免疫荧光及实时荧光定量PCR检测各组小鼠皮损内IL-21表达情况。随后另将10只雄性BALB/c小鼠随机分为IL-21注射组和灭菌水注射组,连续造模4 d。取小鼠注射部位皮损观察组织病理学改变,免疫荧光检测角蛋白(keratin, K)17和实时荧光定量PCR检测IL-17A表达。结果 咪喹莫特诱导小鼠出现典型的银屑病临床及组织病理表现,模型组小鼠PASI评分较对照组升高(P<0.000 1),小鼠皮损内IL-21表达水平上调(P<0.000 1),IL-21表达细胞数目增多;与灭菌水灌胃组相比,阿维A灌胃后小鼠组织病理改善,PASI评分下降(P<0.01),小鼠皮损内IL-21表达水平降低(P<0.000 1),IL-21表达细胞数目减少。相关性分析显示IL-21与小鼠PASI评分呈正相关(r=0.820 0,P<0.000 1)。与灭菌水注射组相比,IL-21注射导致小鼠表皮增厚,小鼠皮损内K17及IL-17A表达升高(P<0.01,P<0.000 1)。结论 IL-21在银屑病小鼠皮损中表达水平升高,与小鼠银屑病严重程度呈正相关;IL-21促进角质形成细胞角蛋白17表达水平升高,同时上调IL-17A表达,加重小鼠银屑病炎症反应。

Objective To study the expression characteristics of interleukin(IL)-21 in psoriasis mouse lesions and its role in the pathogenesis of psoriasis.Methods Twenty male BALB/C mice were randomly divided into the control group, model group, acitretin gavage group and sterilized water gavage group.The psoriasis model was established by the application of 5% imiquimod cream on the back of mice. After 7 days of continuous modeling, PASI scores of mice in each group were calculated.Histopathological changes were observed in skin lesions of mice, and IL-21 expression in each group was detected by immunofluorescence and real-time fluorescence quantitative PCR(RT-PCR).Ten male BALB/C mice were then randomly divided into the IL-21 injection group and the sterilized water injection group for continuous modeling for 4 days.The histopathological changes of skin lesions at the injection site were observed, and the expression of keratin(K) 17 and IL-17 A was detected by immunofluorescence and RT-PCR,respectively.Results Typical clinical and histopathological manifestations of psoriasis were observed after the application of the imiquimod.PASI score and IL-21 expression of mice in the model group were significantly higher than in the control group.Immunofluorescence analysis showed that the number of IL-21 expressing cells increased in skin lesions of psoriasis mice.Compared with the sterilized water gavage group, the histopathological manifestations of psoriasis mice were relieved after administration of acitretin, with decreased PASI scores(P<0.01) and expression of IL-21(P<0.000 1).The number of IL-21-expressing cells also decreased.Correlation analysis showed that IL-21 was positively correlated with the PASI scores(r=0.820 0,P<0.000 1).Compared with the sterilized water injection group, injection of IL-21 increased the thickness of the epidermis(P<0.05),the expression of K17(P<0.01) and IL-17 A(P<0.0001) in mice.Conclusion The expression of IL-21 is increased in psoriatic mice, which is positively correlated with the severity of psoriasis.In addition, IL-21 promotes the expression of keratin(K)17 and up-regulates the expression of IL-17 A,which aggravates the inflammatory of psoriasis in mice.