Paeoniflorin Ameliorates Experimental Autoimmune Encephalomyelitis via Inhibition of Dendritic Cell Function and Th17 Cell Differentiation.
Paeoniflorin (PF) is a monoterpene glycoside and exhibits multiple effects, including anti-inflammation and immunoregulation. To date, the effect of PF on multiple sclerosis (MS) has not been investigated. In this study, we investigated the effect of PF in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. After administered with PF, the onset and clinical symptoms of EAE mice were significantly ameliorated, and the number of Th17 cells infiltrated in central nervous system (CNS) and spleen was also dramatically decreased. Instead of inhibiting the differentiation of Th17 cells directly, PF influenced Th17 cells via suppressing the expression of costimulatory molecules and the production of interlukin-6 (IL-6) of dendritic cells (DCs) in vivo and in vitro, which may be attributable to the inhibition of IKK/NF-κB and JNK signaling pathway. When naïve CD4+T cells were co-cultured with PF-treated dendritic cells under Th17-polarizing condition, the percentage of Th17 cells and the phosphorylation of STAT3 were decreased, as well as the mRNA levels of IL-17, RORα, and RORγt. Our study provided insights into the role of PF as a unique therapeutic agent for the treatment of multiple sclerosis and illustrated the underlying mechanism of PF from a new perspective.
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.|Department of Clinical Immunology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Han
H
Zhang
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Yuanyuan
Y
Qi
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Yuanyang
Y
Yuan
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Li
L
Cai
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Haiyan
H
Xu
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Lili
L
Zhang
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Bing
B
Su
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Hong
H
Nie
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D016328:NF-kappa B / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006027:Glycosides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017077:Culture Media, Conditioned; D005960:Glucosides; D020381:Interleukin-17; D015850:Interleukin-6; D048670:MAP Kinase Kinase 4; D039821:Monoterpenes; D016328:NF-kappa B; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539739:Rora protein, mouse; C539901:Rorc protein, mouse; C015423:peoniflorin; D006027:Glycosides