Blocking effect of an immuno-suppressive agent, cynarin, on CD28 of T-cell receptor.

Abstract:

PURPOSE:Cynarin, a potential immunosuppressant that blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells, was found in Echinacea purpurea by a new pharmaceutical screening method: After Flowing Through Immobilized Receptor (AFTIR; Dong et al., J Med Chem, 49: 1845-1854, 2006). This Echinacea component is the first small molecule that is able to specifically block "signal 2" of T-cell activation. METHODS:In this study, we used the AFTIR method to further confirm that cynarin effectively blocked the binding between CD80 of B-cells and CD28 of T-cells, and provide details of its mechanism of action. RESULTS:The experimental results showed that cynarin blocked about 87% of the CD28-dependent "signal 2" pathway of T-cell activation under the condition of one to one ratio of T-cell and B-cell in vitro. Theoretical structure modeling showed that cynarin binds to the "G-pocket" of CD28 (Evans et al., Nat Immunol, 6:271-279, 2005), and thus interrupts the site of interaction between CD28 and CD80. CONCLUSIONS:These results confirm both that AFTIR is a promising method for screening selective active compounds from herbal medicine and that cynarin has great potential as an immuno-suppressive agent.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Dong GC,Chuang PH,Chang KC,Jan PS,Hwang PI,Wu HB,Yi M,Zhou HX,Chen HM

doi

10.1007/s11095-008-9754-5

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

375-81

issue

2

eissn

0724-8741

issn

1573-904X

journal_volume

26

pub_type

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