期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 123, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2023.110787
关键词
TPN10518; Th1/Th17 cells; AP1; Experimental autoimmune encephalomyelitis
TPN10518, an artemisinin derivative, protects against experimental autoimmune encephalomyelitis (EAE) by inhibiting the production of Th1 and Th17 cells through AP1 downregulation. This study suggests that TPN10518 could be a potential drug for the treatment of multiple sclerosis (MS).
Multiple sclerosis (MS) is one of the most common autoimmune diseases of central nervous system (CNS) demyelination. Experimental autoimmune encephalomyelitis (EAE) is the most classic animal model for simulating the onset of clinical symptoms in MS. Previous research has reported the anti-inflammatory effects of artemisinin on autoimmune diseases. In our study, we identified a novel small molecule, TPN10518, an artemisinin derivative, which plays a protective role on the EAE model. We found that TPN10518 reduced CNS inflammatory cell infiltration and alleviated clinical symptoms of EAE. In addition, TPN10518 downregulated the production of Th1 and Th17 cells in vivo and in vitro, and decrease the levels of related chemokines. RNA-seq assay combined with the experimental results demonstrated that TPN10518 lowered the mRNA and protein levels of the AP1 subunits c-Fos and c-Jun in EAE mice. It was further confirmed that TPN10518 was dependent on AP1 to inhibit the differentiation of Th1 and Th17 cells. The results suggest that TPN10518 reduces the production of Th1 and Th17 cells through inhibition of AP1 to alleviate the severity of EAE disease. It is expected to be a potential drug for the treatment of MS.
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