Abstract：
OBJECTIVE: Psoriasis is a prevalent chronic inflammatory skin disease in humans that is characterized by frequent relapses and challenging to cure. WB518 is a novel small molecule compound with an undisclosed structure. Therefore, our study aimed to investigate the therapeutic potential of WB518 in vitro and in vivo for the treatment of psoriasis, specifically targeting the abnormal proliferation, aberrant differentiation of epidermal keratinocytes, and pathogenic inflammatory response.
METHODS: We employed dual luciferase reporter assay to screen compounds capable of inhibiting STAT3 gene transcription. Flow cytometry was utilized to analyze CD3-positive cells. Protein and mRNA levels were assessed through Western blotting, immunofluorescence, immunohistochemistry, and real-time PCR. Cell viability was measured using the MTS assay, while in vivo models of psoriasis induced by IMQ and TPA were employed to study the anti-psoriasis effect of WB518.
RESULTS: WB518 was found to significantly reduce the mRNA and protein levels of Keratin 17 (K17) in HaCaT cells by inhibiting the phosphorylation of STAT3 Tyr705 (Y705). In the IMQ and TPA-induced psoriasis mouse model, WB518 effectively improved scaling, epidermal hyperplasia, and inflammation. WB518 also suppressed the expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, and IL-23. Furthermore, WB518 decreased the proportion of CD3-positive cells in the psoriatic skin of mice.
CONCLUSIONS: WB518 exhibits promising potential as a treatment candidate for psoriasis.
METHODS: We employed dual luciferase reporter assay to screen compounds capable of inhibiting STAT3 gene transcription. Flow cytometry was utilized to analyze CD3-positive cells. Protein and mRNA levels were assessed through Western blotting, immunofluorescence, immunohistochemistry, and real-time PCR. Cell viability was measured using the MTS assay, while in vivo models of psoriasis induced by IMQ and TPA were employed to study the anti-psoriasis effect of WB518.
RESULTS: WB518 was found to significantly reduce the mRNA and protein levels of Keratin 17 (K17) in HaCaT cells by inhibiting the phosphorylation of STAT3 Tyr705 (Y705). In the IMQ and TPA-induced psoriasis mouse model, WB518 effectively improved scaling, epidermal hyperplasia, and inflammation. WB518 also suppressed the expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, and IL-23. Furthermore, WB518 decreased the proportion of CD3-positive cells in the psoriatic skin of mice.
CONCLUSIONS: WB518 exhibits promising potential as a treatment candidate for psoriasis.
摘要：
目的：银屑病是人类常见的慢性炎症性皮肤病，其特点是频繁复发，难以治愈。WB518是具有未公开结构的新型小分子化合物。因此,我们的研究旨在探讨WB518在体外和体内治疗银屑病的治疗潜力，专门针对异常增殖，表皮角质形成细胞的异常分化，和致病性炎症反应。
方法:我们采用双荧光素酶报告基因测定来筛选能够抑制STAT3基因转录的化合物。流式细胞术用于分析CD3阳性细胞。蛋白质和mRNA水平通过蛋白质印迹进行评估，免疫荧光，免疫组织化学，和实时PCR。使用MTS测定法测量细胞活力，同时采用IMQ和TPA诱导的银屑病体内模型来研究WB518的抗银屑病作用。
结果：发现WB518通过抑制STAT3Tyr705（Y705）的磷酸化，显着降低HaCaT细胞中角蛋白17（K17）的mRNA和蛋白质水平。在IMQ和TPA诱导的银屑病小鼠模型中,WB518有效改善了缩放，表皮增生,和炎症。WB518还抑制炎症细胞因子的表达，如白细胞介素（IL）-1β，IL-6、IL-17和IL-23。此外，WB518降低了小鼠银屑病皮肤中CD3阳性细胞的比例。
结论：WB518作为治疗银屑病的候选药物显示出有希望的潜力。
方法:我们采用双荧光素酶报告基因测定来筛选能够抑制STAT3基因转录的化合物。流式细胞术用于分析CD3阳性细胞。蛋白质和mRNA水平通过蛋白质印迹进行评估，免疫荧光，免疫组织化学，和实时PCR。使用MTS测定法测量细胞活力，同时采用IMQ和TPA诱导的银屑病体内模型来研究WB518的抗银屑病作用。
结果：发现WB518通过抑制STAT3Tyr705（Y705）的磷酸化，显着降低HaCaT细胞中角蛋白17（K17）的mRNA和蛋白质水平。在IMQ和TPA诱导的银屑病小鼠模型中,WB518有效改善了缩放，表皮增生,和炎症。WB518还抑制炎症细胞因子的表达，如白细胞介素（IL）-1β，IL-6、IL-17和IL-23。此外，WB518降低了小鼠银屑病皮肤中CD3阳性细胞的比例。
结论：WB518作为治疗银屑病的候选药物显示出有希望的潜力。
