Received for publication March 29, 2006.
Revised June 1, 2006.
Accepted for publication June 1, 2006.

Periplocoside E Inhibits Experimental Allergic Encephalomyelitis by Suppressing IL-12-Dependent CCR5 Expression and IFN-gamma-Dependent CXCR3 Expression in T Lymphocytes

Abstract

Periplocoside E (PSE) was found to inhibit primary T cells 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 glycoprotein (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 cords histopathology analysis demonstrated that the therapeutic effect of PSE was associated with reduced mononuclear cell infiltration and CNS inflammation. As RT-PCR 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 to T cells from normal mice. However, CCR5 and CXCR3 expressions were suppressed in T cells from PSE-treated mice. In vitro study also demonstrated PSE inhibited IFN-gamma-dependent CXCR3 expression in T cells through suppressing TCR-ligation induced IFN-gamma production while inhibited 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⁺ cell was decreased in spinal cords from PSE-treated mice. These findings suggest the potential therapeutic effect of PSE on Multiple sclerosis.

Key words: CCR5, CXCR3, Experimental Allergic Encephalomyelitis, Periploca sepium, Periplocoside E, T lymphocytes

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