Obaculactone suppresses Th1 effector cell function through down-regulation of T-bet and prolongs skin graft survival in mice.

Obaculactone suppresses Th1 effector cell function through down-regulation of T-bet and prolongs skin graft survival in mice.
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Obaculactone 通过下调 T-bet 抑制 Th1 效应细胞功能,并延长小鼠皮肤移植物的存活时间。

DOI:
10.1016/j.bcp.2010.03.028
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发表时间:
2010-07
影响因子:
5.8
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
作者:

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同种异体移植排斥反应主要是Th1免疫反应。在这项研究中,我们证明了从柑橘类水果中提取的一种天然化合物--杆菌内酯,在移植后而不是移植前治疗时,可以延长小鼠的皮肤移植存活时间。此外,杆菌内酯还能抑制Th1型细胞因子干扰素-γ以及促炎细胞因子IL-2、肿瘤坏死因子α和IL-6的产生。同时,IL-10的产生明显上调。奥巴拉内酯可显著提高小鼠外周血中CD4+CD25+Foxp3+Treg细胞的百分率,但对其抑制功能无明显影响。体外和体内试验表明,细菌内酯下调了Th1效应细胞中T-bet的表达。综上所述,独特的免疫调节特性可能使杆菌内酯有资格作为一种假定的治疗化合物,用于治疗Th1驱动的疾病,包括移植排斥反应。
Allograft rejection is a predominantly Th1 immune response. In this study, we showed that obaculactone, a natural compound derived from citrus fruit, prolonged skin graft survival in mice when treated after but not before transplantation. Furthermore, obaculactone inhibited alloantigen-specific production of Th1 cytokine IFN-γ as well as proinflammatory cytokine IL-2, TNFα and IL-6. In parallel, IL-10 production was markedly up-regulated. Obaculactone significantly enhanced the percentage of CD4+CD25+Foxp3+Treg cells in the CD4+splenocytes without any effect on their inhibitory function. In vitro and in vivo tests showed obaculactone down-regulated T-bet expression in Th1 effector cells. Taken together, the unique immunomodulatory properties might qualify obaculactone as a putative, therapeutic compound for the treatment of Th1-driven diseases, including transplant rejection.
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