期刊
PHARMACOLOGICAL RESEARCH
卷 169, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.105678
关键词
Triptolide; LLDT-8; Psoriasis; IL-36 alpha; IL-36 alpha pathway; Inflammation
资金
- National Natural Science Foundation of China [82003762]
Triptolide derivative LLDT-8 demonstrated significant alleviation of IMQ-induced psoriasis-like skin inflammation by suppressing the IL-36 alpha signaling pathway, indicating its potential as a drug for psoriasis treatment.
Triptolide has shown a good immunosuppressive effect on autoimmune diseases. However, the toxicity limited its widely clinical practice. In this study, we investigated the effects and underlying mechanisms of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, on a murine psoriasis-like dermatitis model and related cell lines. Here, we showed that LLDT-8 significantly attenuated symptoms of psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7 agonist) by reducing the psoriasis area and severity index (PASI) score and inflammatory parameters. The action of LLDT-8 was involved in down-regulated interleukin (IL)-36 alpha expression and blocked IL-36 alpha pathway by LC-MS-based label-free quantitative (LFQ) proteomic approach and further experiments. Meanwhile, we observed that LLDT-8 significantly inhibited the expression of IL-36 alpha in R837-treated bone marrow-derived dendritic cells (BMDCs). In conclusion, LLDT-8 notably alleviated IMQ-induced psoriasis-like skin inflammation via suppressing the IL-36 alpha signaling pathway, suggesting LLDT-8 might be a potential drug for the treatment of psoriasis.
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