蛋白酶抑制剂调节各种生物过程并防止宿主组织/器官损伤。蛋白酶的特异性抑制/调节对于治疗几种疾病在临床上是有价值的。牛皮癣影响身体四肢和头皮的皮肤,半胱氨酸和丝氨酸蛋白酶对皮肤炎症发展的贡献是有据可查的。来自蜱的半胱氨酸蛋白酶抑制剂具有很高的特异性,选择性,和对其靶蛋白酶的亲和力,是有效的免疫调节剂。然而,它们对银屑病发病机制的潜在治疗作用尚待确定。因此,我们测试了四种蜱类半胱氨酸抑制素(唾液酸抑素L,唾液酸抑素L2,Iristatin,和Mialostatin)在最近开发的,先天免疫依赖性甘露聚糖诱导的银屑病模型。我们探讨了蛋白酶抑制剂对临床症状和组织学特征的影响。此外,免疫细胞的数量和百分比(树突状细胞,中性粒细胞,巨噬细胞,和γδT细胞)通过流式细胞术,免疫荧光/免疫组织化学和,促炎细胞因子(TNF-a,IL-6,IL-22,IL-23和IL-17家族)通过qPCR进行分析,使用皮肤,脾,脾和淋巴结样本.Tick蛋白酶抑制剂可显着减少牛皮癣症状和疾病表现,但对炎症反应和免疫细胞群产生不同的影响。提示这些抑制剂对牛皮癣样炎症的不同作用方式。因此,我们的研究表明,第一次,蜱源性蛋白酶抑制剂治疗患者皮肤炎症的有效性。
Protease inhibitors regulate various biological processes and prevent host tissue/organ damage. Specific inhibition/regulation of proteases is clinically valuable for treating several diseases. Psoriasis affects the skin in the limbs and scalp of the body, and the contribution of cysteine and serine proteases to the development of skin inflammation is well documented. Cysteine protease inhibitors from ticks have high specificity, selectivity, and affinity to their target proteases and are efficient immunomodulators. However, their potential therapeutic effect on psoriasis pathogenesis remains to be determined. Therefore, we tested four tick cystatins (Sialostatin L, Sialostatin L2, Iristatin, and Mialostatin) in the recently developed, innate immunity-dependent mannan-induced psoriasis model. We explored the effects of protease inhibitors on clinical symptoms and histological features. In addition, the number and percentage of immune cells (dendritic cells, neutrophils, macrophages, and γδT cells) by flow cytometry, immunofluorescence/immunohistochemistry and, the expression of pro-inflammatory cytokines (TNF-a, IL-6, IL-22, IL-23, and IL-17 family) by qPCR were analyzed using skin, spleen, and lymph node samples. Tick protease inhibitors have significantly decreased psoriasis symptoms and disease manifestations but had differential effects on inflammatory responses and immune cell populations, suggesting different modes of action of these inhibitors on psoriasis-like inflammation. Thus, our study demonstrates, for the first time, the usefulness of tick-derived protease inhibitors for treating skin inflammation in patients.