Department of Dermatology, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Immun Inflamm Dis. 2023 Jul;11(7):e877. doi: 10.1002/iid3.877.
A recent study confirmed that thiolutin (THL), as a potent inflammasome inhibitor, plays a promising therapeutic role in multiple inflammatory disease models. However, the effect of THL on psoriasis has not been reported so far.
A psoriasiform dermatitis model was prepared by applying 5% imiquimod (IMQ) cream on mice. A total of 36 mice were randomly divided into six groups: control, model, model + THL-L/M/H (THL, 1/2.5/5 mg/kg/day), model + methotrexate (1 mg/kg/day). Psoriasis area and severity index (PASI) scores were observed and calculated. The histological changes in skin, liver, and kidney tissues were observed by hematoxylin and eosin staining. Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and blood creatinine were measured by automatic biochemistry analyzer. The size of the spleens was determined, and the proportion of Foxp3 + CD4+ regulatory T (Treg) cells in the spleens was tested by flow cytometry. The proinflammatory factors and nucleotide oligomerization domain nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome protein levels were examined by reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry, respectively.
THL administration preeminently reduced the thickness, scaling, and erythema of the skin lesions, alleviated IMQ-induced psoriasiform lesions in mice, reduced the PASI score, and ameliorated histopathological changes in mouse skin. The spleen index was decreased by almost half and the proportion of Foxp3 + CD4+ Treg cells was increased after intervention by THL. THL intervention did not affect liver and kidney function, but decreased the expression levels of proinflammatory factors and NLRP3 inflammasome in the skin of psoriatic mice.
THL may alleviate IMQ-induced psoriasis-like manifestations in mice by inhibiting NLRP3 inflammasome.
最近的一项研究证实，硫嘌呤（THL）作为一种有效的炎症小体抑制剂，在多种炎症性疾病模型中发挥着有前途的治疗作用。然而，THL 对银屑病的影响迄今尚未报道。
通过在小鼠上涂抹 5%咪喹莫特（IMQ）乳膏制备银屑病样皮炎模型。将 36 只小鼠随机分为六组：对照组、模型组、模型+THL-L/M/H（THL，1/2.5/5mg/kg/天）、模型+甲氨蝶呤（1mg/kg/天）。观察并计算银屑病面积和严重程度指数（PASI）评分。通过苏木精和伊红染色观察皮肤、肝脏和肾脏组织的组织学变化。通过自动生化分析仪测量丙氨酸氨基转移酶、天冬氨酸氨基转移酶、血尿素氮和血肌酐。测定脾脏大小，并通过流式细胞术检测脾脏中 Foxp3+CD4+调节性 T（Treg）细胞的比例。通过逆转录定量聚合酶链反应、酶联免疫吸附试验、Western blot 和免疫组化分别检测促炎因子和核苷酸结合寡聚结构域核苷酸结合寡聚结构域（NOD）样受体蛋白 3（NLRP3）炎症小体蛋白水平。
THL 给药显著减轻了皮肤损伤的厚度、鳞屑和红斑，缓解了 IMQ 诱导的小鼠银屑病样病变，降低了 PASI 评分，并改善了小鼠皮肤的组织病理学变化。THL 干预后，脾脏指数降低近一半，Foxp3+CD4+Treg 细胞的比例增加。THL 干预不影响肝肾功能，但降低了银屑病样小鼠皮肤中促炎因子和 NLRP3 炎症小体的表达水平。
THL 可能通过抑制 NLRP3 炎症小体来缓解 IMQ 诱导的小鼠银屑病样表现。
