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Caffeic Acid Phenethyl Ester Protects against Experimental Autoimmune Encephalomyelitis by Regulating T Cell Activities.

ABSTRACT: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by progressive demyelination and disabling outcomes. CD4+ T cells are the most critical driving factor of relapsing MS, but little improvement has been noted upon deletion of the whole T cell population. Caffeic acid phenethyl ester (CAPE), one of the main active compounds of propolis, exhibits potent antitumour, anti-inflammatory, and antioxidant properties by suppressing nuclear factor-?B (NF-?B) transactivation. To investigate the therapeutic potential of CAPE in MS, we studied the effects of CAPE on cytokine levels, T cells, and NF-?B activities and in an experimental MS animal model. The results showed that cerebrospinal fluid (CSF) from patients with relapsing MS is characterized by increased levels of proinflammatory cytokines/chemokines that preferentially skew towards T helper 1 (Th1) cytokines. In vitro studies demonstrated that CAPE not only inhibited T cell proliferation and activation but also effectively modulated T cell subsets. Under both Th0- and Th1-polarizing conditions, the proportion of CD4+IFN-? + cells was downregulated, while CD4+Foxp3+ cells were increased. Moreover, nuclear translocation of NF-?B p65 was inhibited by CAPE. In a murine experimental autoimmune encephalomyelitis model, prophylactic treatment with CAPE significantly decreased the disease incidence and severity. Compared to the vehicle group, mice pretreated with CAPE showed diminished inflammatory cell infiltration, microglia/macrophage activation, and demyelination injury. Additionally, CAPE pretreatment reduced the level of Th1 cells in both spleen and the CNS and increased regulatory T cells (Tregs) in the CNS. In conclusion, our results highlight the potential merit of CAPE in suppressing T cell activity mainly through targeting the pathogenic Th1 lineage, which may be beneficial for MS treatment.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC7568814 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Caffeic Acid Phenethyl Ester Protects against Experimental Autoimmune Encephalomyelitis by Regulating T Cell Activities.

Zhou YiFan Y Wang Jingqi J Chang Yanyu Y Li Rui R Sun Xiaobo X Peng Lisheng L Zheng WenHua W Qiu Wei W

Oxidative medicine and cellular longevity 20201009

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by progressive demyelination and disabling outcomes. CD4<sup>+</sup> T cells are the most critical driving factor of relapsing MS, but little improvement has been noted upon deletion of the whole T cell population. Caffeic acid phenethyl ester (CAPE), one of the main active compounds of propolis, exhibits potent antitumour, anti-inflammatory, and antioxidant properties by suppressing n ...[more]

PMID: 33133349

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Project description:Background/Aims:Increasing evidence have associated mitochondrial dysfunction and reactive oxygen species (ROS) generation to neuron loss in multiple sclerosis (MS). PGC-1α regulates mitochondrial biogenesis and respiration and plays a pivotal role in modulating ROS levels. Here, we investigated the potential function of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) in the mammalian MS disease model, EAE experimental autoimmune encephalomyelitis (EAE). Methods:We used WT mice to evaluate the change of PGC during the course of EAE. The transgenic mice with neuron-specific overexpression of PGC-1α was applied to explore how PGC1 in neuron affects EAE outcome. A neuronal cell line of lentivirus transfection leading to PGC-1α markedly increased was applied to verify the protective effects of PGC1 in neurons. RNA-seq was employed to explore the potential target genes and signaling pathways. Results: We observed that PGC-1α were decreased at 13d, continuously decreased at 20d, then mildly increased at 30d in wild-type (WT) EAE mice, which is accompanied with alterations of mitochondrial antioxidants SOD2, Prx3, Trx2 and UCP4,5. Our study revealed that PGC-1αf/f Eno2-Cre mice improved EAE clinical symptoms, ameliorated inflammation and demyelination in spinal cords, increased mitochondrial antioxidants SOD2, Prx3, Trx2 and UCPs, reduced the production of ROS and inhibited the apoptotic pathways. In addition, PGC-1αf/f Eno2-Cre mice showed decreased apoptotic neurons compared with the WT EAE mice. In vitro, overexpressing PGC-1α by lentivirus transfection revealed similar results with that of in vivo by using NSC-34 cells treated with 1mg/ml lipopolysaccharide (LPS). Furthermore, RNA-seq analysis showed that apoptotic processes were significantly enriched in the top 10 significant GO terms of differentially expressed (DE) gene and apotosis pathway was significantly enriched in KEGG pathway analysis. Conclusion: Taken together, our findings indicate that upregulation of neuronal PGC-1α protected neuron apotosis in EAE and in vitro.

Dataset Information

Caffeic Acid Phenethyl Ester Protects against Experimental Autoimmune Encephalomyelitis by Regulating T Cell Activities.

Publications

Caffeic Acid Phenethyl Ester Protects against Experimental Autoimmune Encephalomyelitis by Regulating T Cell Activities.

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