(5R)-5-hydroxytriptolide inhibits IFN-g-related signaling
文献类型：期刊论文
| 作者 | Yuanchao Li; Xiaoyu Li; Jianping Zuo ; Ru Zhou; Junxia Wang; Wei Tang; Peilan He; Yifu Yang
|
| 刊名 | Acta Pharmacologica Sinica
 |
| 出版日期 | 2006 |
| 卷号 | 27期号:12页码:1616 |
| 关键词 | (5R)-5-hydroxytriptolide IFN-g MAPK chemokine |
| ISSN号 | 1671-4083 |
| 英文摘要 | Aim: (5R)-5-hydroxytriptolide (LLDT-8) displayed anti-arthritis and anti-allogenic transplantation rejection activities in our previous studies. Here, we aim to further clarify the effect of LLDT-8 on the pro-inflammatory cytokine IFN-g. Methods: T cells were activated with anti-CD3 antibody or concanavalin A (ConA). The expression of cell surface molecules was detected with flow cytometry. Cells were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) to test cell division. IFN-g production was determined by enzyme-linked immunosorbent assay. Cell proliferation was evaluated by 3H-thymidine uptake. Mice were immunized with ovalbumin to assess the in vivo immune response. RT-PCR and Real-time PCR were applied to determine the mRNA expression. The protein phosphorylation levels were detected by Western immunoblot assay. Results: LLDT-8 at 100 nmol/L did not change the CD25, CD69, and CD154 expressions in anti-CD3-stimulated T cells. LLDT-8 markedly blocked the cell division of CD4 and CD8 T cells after ConA stimulation. LLDT-8 inhibited T cell-derived IFN-g production. Moreover, LLDT-8 suppressed the ovalbumin-specific T cell proliferation and IFN-g generation. In anti-CD3-activated T cells, LLDT-8 abrogated the mRNA expression of signal transducer and activator of transcription1 (STAT1), T-box transcription factor, IL-12 receptor b2, STAT4, and interferon regulatory factor 1 in the IFN-g expression pathway. Western blot analysis showed that LLDT-8 blocked the phosphorylation levels of extracellular signal-regulated kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in anti-CD3 plus anti-CD28-activated T cells. In addition, LLDT-8 reduced the transcripts of macrophage inflammatory protein (Mip)-1a, Mip-1b, regulated upon activation normally T-cell expressed and secreted, inducible protein-10, IFN-inducible T cell a chemoattractant, and monokine induced by IFN-g in IFN-g-stimulated murine macrophage cell line Raw 264.7 cells. Conclusion: LLDT-8 was a potential inhibitor for IFN-g-associated signaling. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/293964]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Yuanchao Li,Xiaoyu Li,Jianping Zuo,et al. (5R)-5-hydroxytriptolide inhibits IFN-g-related signaling[J]. Acta Pharmacologica Sinica,2006,27(12):1616. |
| APA | Yuanchao Li.,Xiaoyu Li.,Jianping Zuo.,Ru Zhou.,Junxia Wang.,...&Yifu Yang.(2006).(5R)-5-hydroxytriptolide inhibits IFN-g-related signaling.Acta Pharmacologica Sinica,27(12),1616. |
| MLA | Yuanchao Li,et al."(5R)-5-hydroxytriptolide inhibits IFN-g-related signaling".Acta Pharmacologica Sinica 27.12(2006):1616. |
入库方式： OAI收割
来源：上海药物研究所
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