中国药理学通报2018，Vol.34Issue(7)：925-933,9.DOI:10.3969/j.issn.1001-1978.2018.07.009
苯并恶唑衍生物PO-291抑制活化T细胞增殖与功能的机制研究
Research on principle of benzoxazole derivative PO-291 inhibiting T cell proliferation
摘要
Abstract
Objective To investigate the immunosup-pressive activity of benzoxazole derivative PO-291 in inhibiting human activated T cell proliferation and function. Methods Human T cells were isolated and purified by the immunomagnetic microbeads and acti-vated by anti-CD3/anti-CD28 mAbs or alloantigen. Cell proliferation, the expression of CD25 and CD69, cell cycle and apoptosis were measured by flow cytome-try. Secretion levels, including IL-2, IL-4, IL-6, IL-10, IL-17 and IFN-γ were determined by ELISA. The expression and phosphorylation of STAT5 and p70S6K of activated T cells were detected by Western blot. Re-sults PO-291 significantly inhibited human T cell proliferation with anti-CD3/anti-CD28 mAbs or alloan-tigen stimulation without obvious cytotoxicity. PO-291 did not affect CD25, CD69 and IL-2 expression, but induced T cell cycle arrest in G0/G1 phase. PO-291 significantly inhibited IL-17, IFN-γ and IL-6 expres-sion, but not IL-2, IL-4 and IL-10. PO-291 did not affect STAT5 and p70S6K expression, but inhibited STAT5 phosphorylation and enhanced p70S6K phos-phorylation. Conclusions PO-291 inhibits human ac-tivated T cell proliferation by affecting the JAK3/STAT5 pathway. PO-291 represents a potential lead compound for the design and development of new im-munosuppressive drugs for the treatment of organ trans-plantation and autoimmune diseases.关键词
PO-291/免疫抑制剂/T细胞增殖/细胞因子/流式细胞术/JAK3Key words
PO-291/immunosuppressant/T cell pro-liferation/cytokines/flow cytometry/JAK3分类
医药卫生引用本文复制引用
王思雨,熊静,周宏,罗兴燕,刘阳,赖翼..苯并恶唑衍生物PO-291抑制活化T细胞增殖与功能的机制研究[J].中国药理学通报,2018,34(7):925-933,9.基金项目
国家自然科学基金资助项目( No 81302786) （ No 81302786）
成都医学院自然基金项目(No CYTD15-01,CYZ15-13) （No CYTD15-01,CYZ15-13）
大学生国家创新项目(No 201513705040) （No 201513705040）
