QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jpet.106.105445v1 318/3/1153    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, Y.-N. Articles by Zuo, J.-P. Search for Related Content PubMed PubMed Citation Articles by Zhu, Y.-N. Articles by Zuo, J.-P. Pubmed/NCBI databases Substance via MeSH

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

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

Laboratories of Immunopharmacology (Y.-N.Z., X.-G.Z., Y.-F.Y., Y.-F.F., J.N., W.T., J.-P.Z.) and Natural Products Chemistry (J.-Q.F., Q.-F.L., W.-M.Z.), State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China; and Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (J.-P.Z.)

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)--dependent CXCR3 expression in T cells through suppressing T-cell receptor (TCR) ligation-induced IFN- 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.

Address correspondence to: Dr. Jian-Ping Zuo, Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China. E-mail: jpzuo{at}mail.shcnc.ac.cn

This article has been cited by other articles:

				A. Cabrelle, I. Dell'Aica, L. Melchiori, S. Carraro, E. Brunetta, R. Niero, E. Scquizzato, G. D'Intino, L. Calza, S. Garbisa, et al. Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease J. Leukoc. Biol., January 1, 2008; 83(1): 212 - 219. [Abstract] [Full Text] [PDF]

				M. Muller, S. L. Carter, M. J. Hofer, P. Manders, D. R. Getts, M. T. Getts, A. Dreykluft, B. Lu, C. Gerard, N. J. C. King, et al. CXCR3 Signaling Reduces the Severity of Experimental Autoimmune Encephalomyelitis by Controlling the Parenchymal Distribution of Effector and Regulatory T Cells in the Central Nervous System J. Immunol., September 1, 2007; 179(5): 2774 - 2786. [Abstract] [Full Text] [PDF]