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Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Periplocoside E Inhibits Experimental Allergic Encephalomyelitis by Suppressing Interleukin 12-Dependent CCR5 Expression and Interferon-γ-Dependent CXCR3 Expression in T Lymphocytes

Yi-Na Zhu, Xiang-Gen Zhong, Jia-Quan Feng, Yi-Fu Yang, Yun-Feng Fu, Jia Ni, Qun-Fang Liu, Wei Tang, Wei-Min Zhao and Jian-Ping Zuo
Journal of Pharmacology and Experimental Therapeutics September 2006, 318 (3) 1153-1162; DOI: https://doi.org/10.1124/jpet.106.105445
Yi-Na Zhu
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Xiang-Gen Zhong
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Jia-Quan Feng
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Yi-Fu Yang
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Yun-Feng Fu
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Jia Ni
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Qun-Fang Liu
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Wei Tang
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Wei-Min Zhao
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Jian-Ping Zuo
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Abstract

Periplocoside E (PSE) was found to inhibit primary T-cell activation in our previous study. Now we examined the effect and mechanisms of PSE on the central nervous system (CNS) demyelination in experimental allergic encephalomyelitis (EAE). C57BL/6 mice immunized with myelin oligodendrocyte glyco-protein (MOG) were treated with PSE following immunization and continued throughout the study. The effect on the progression of EAE and other relevant parameters were assessed. PSE reduced the incidence and severity of EAE. Spinal cord histopathology analysis showed that the therapeutic effect of PSE was associated with reduced mononuclear cell infiltration and CNS inflammation. As reverse transcription-polymerase chain reaction analysis showed, PSE decreased the CD4+, CD8+, and CD11b+ cell infiltration. T cells from lymph nodes of MOG-immunized mice expressed enhanced levels of CCR5 and CXCR3 mRNA compared with T cells from normal mice. However, CCR5 and CXCR3 expressions were suppressed in T cells from PSE-treated mice. In vitro study also showed PSE inhibited interferon (IFN)-γ-dependent CXCR3 expression in T cells through suppressing T-cell receptor (TCR) ligation-induced IFN-γ production, whereas it inhibited interleukin (IL)-12-dependent CCR5 expression through suppressing IL-12 reactivity in TCR-triggered T cells. As a result, the initial influx of T cells into CNS was inhibited in PSE-treated mice. The consequent activation of macrophages/microglia cells was inhibited in spinal cord from PSE-treated mice as determination of chemokine expressions (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10). Consistently, the secondary influx of CD4+, CD8+, and CD11b+ cells was decreased in spinal cords from PSE-treated mice. These findings suggest the potential therapeutic effect of PSE on multiple sclerosis.

Footnotes

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.106.105445.

  • ABBREVIATIONS: EAE, experimental allergic encephalomyelitis; CNS, central nervous system; MS, multiple sclerosis; BBB, blood-brain barrier; IL, interleukin; CCR, CC chemokine receptor; CCL, CC chemokine ligand; CXCR, CXC chemokine receptor; CXCL, CXC chemokine ligand; IFN, interferon; MOG, myelin oligodendrocyte glycoprotein; PSE, periplocoside E; CFA, Complete Freund's adjuvant; ELISA, enzyme-linked immunosorbent assay; mAb, monoclonal antibody; PBS, phosphate-buffered saline; p.i., postimmunization; APC, antigen-presenting cell(s); Ig, immunoglobulin; RT-PCR, reverse transcription-polymerase chain reaction; TCR, T-cell receptor; MIP, macrophage inflammatory protein.

  • ↵ Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ↵1 These authors contributed equally to this work.

    • Received March 29, 2006.
    • Accepted June 1, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 385 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 3
1 Jun 2023
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Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Periplocoside E Inhibits Experimental Allergic Encephalomyelitis by Suppressing Interleukin 12-Dependent CCR5 Expression and Interferon-γ-Dependent CXCR3 Expression in T Lymphocytes

Yi-Na Zhu, Xiang-Gen Zhong, Jia-Quan Feng, Yi-Fu Yang, Yun-Feng Fu, Jia Ni, Qun-Fang Liu, Wei Tang, Wei-Min Zhao and Jian-Ping Zuo
Journal of Pharmacology and Experimental Therapeutics September 1, 2006, 318 (3) 1153-1162; DOI: https://doi.org/10.1124/jpet.106.105445

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Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Periplocoside E Inhibits Experimental Allergic Encephalomyelitis by Suppressing Interleukin 12-Dependent CCR5 Expression and Interferon-γ-Dependent CXCR3 Expression in T Lymphocytes

Yi-Na Zhu, Xiang-Gen Zhong, Jia-Quan Feng, Yi-Fu Yang, Yun-Feng Fu, Jia Ni, Qun-Fang Liu, Wei Tang, Wei-Min Zhao and Jian-Ping Zuo
Journal of Pharmacology and Experimental Therapeutics September 1, 2006, 318 (3) 1153-1162; DOI: https://doi.org/10.1124/jpet.106.105445
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