UNASSIGNED: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.
UNASSIGNED: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group.
UNASSIGNED: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.
■使用IMQ诱导的银屑病样病变小鼠模型来鉴定TP5的靶标和分子机制。免疫荧光用于鉴定TP5治疗前后T细胞亚群表达的差异。使用蛋白质印迹(WB)评估NF-κB信号传导途径组分的表达的变化。16SrRNA测序和网络药理学用于检测TP5给药前后皮肤菌群的变化。
■体内,TP5减少了IMQ诱导的小鼠背部炎症。H&E染色显示表皮厚度减少和TP5的炎性细胞浸润。Masson染色显示TP5给药后表皮和真皮胶原蛋白浸润减少。免疫组织化学显示TP5处理显著降低IL-17表达。免疫浸润分析的结果显示牛皮癣性病变具有更多的T细胞亚群。根据免疫荧光结果,TP5显著降低了CD4+的比例,Th17,ROR+,和CD8+T细胞。WB显示TP5降低了IMQ诱导的银屑病模型小鼠皮肤组织中NF-κB通路的表达。16SrRNA测序显示伯克霍尔德菌和假单胞菌科假单胞菌显着增加,葡萄球菌科葡萄球菌显着减少,水细菌,Herbaspirillum,和Balneimonas。TP5处理后,Firmicutes主导了皮肤微生物多样性,而拟杆菌,Verrucomicrobia,TM7,变形杆菌,放线菌,酸杆菌,双子座,和其他物种在IMQ组中占主导地位。
■TP5可能通过调节表皮菌群来治疗牛皮癣,降低NF-κB通路表达,影响T细胞亚群。