Serum amyloid A induces interleukin-33 expression through an IRF7-dependent pathway.

Serum amyloid A induces interleukin-33 expression through an IRF7-dependent pathway.
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DOI:
10.1002/eji.201344310
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发表时间:
2014-07
影响因子:
5.4
通讯作者:
Ye, Richard D.
Ye, Richard D.
中科院分区:
医学3区
文献类型:
--
作者:
Sun, Lei;Zhu, Ziyan;Cheng, Ni;Yan, Qian;Ye, Richard D.

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白介素33(IL-33)是一种IL-1家族细胞因子和核警报蛋白,在上皮性屏障组织和人类血管中有结构性表达。然而,关于IL-33在单核细胞和巨噬细胞中的诱导表达却知之甚少,这两种细胞是天然免疫系统中主要的细胞因子产生细胞。在这里,我们报道了急性时相蛋白血清淀粉样蛋白A(SAA)诱导C57BL/6小鼠单核细胞和小鼠巨噬细胞表达IL-33。SAA诱导IL-33基因转录激活,导致IL-33蛋白的核积聚。TLR2是SAA受体之一,主要负责IL-33的诱导。人IL-33启动子的渐进性缺失导致了干扰素调节因子7的两个潜在结合位点的确定,其中一个(−277/−257)被发现对沙门氏菌刺激的IL-33启动子活性具有重要作用。在SAA刺激下,IRF7被招募到IL-33启动子上,沉默THP-1细胞中IRF7的表达可以抑制SAA诱导的IL-33的表达。SAA还促进了TRAF6和IRF7之间的相互作用。综上所述,这些结果证实IRF7是SAA诱导单核细胞和巨噬细胞表达IL-33的关键转录因子。
Interleukin-33 (IL-33), an IL-1 family cytokine and nuclear alarmin, is constitutively expressed in epithelial barrier tissues and human blood vessels. However, little is known about the induced expression of IL-33 in monocytes and macrophages, which are major cytokine-producing cells of the innate immune system. Here we report the induction of IL-33 expression in both human monocytes and mouse macrophages from C57BL/6 mice by the acute-phase protein serum amyloid A (SAA). SAA induced transcriptional activation of the IL-33 gene, resulting in nuclear accumulation of the IL-33 protein. TLR2, one of the SAA receptors, was primarily responsible for the induction of IL-33. Progressive deletion of the human IL-33 promoter led to the identification of two potential binding sites for interferon regulatory factor 7 (IRF7), one of which (−277/−257) was found to be important for SAA-stimulated IL-33 promoter activity. IRF7 was recruited to the IL-33 promoter upon SAA stimulation, and silencing IRF7 expression in THP-1 cells abrogated SAA-induced IL-33 expression. SAA also promoted an interaction between TRAF6 and IRF7. Taken together, these results identify IRF7 as a critical transcription factor for SAA-induced IL-33 expression in monocytes and macrophages.
DOI: 10.4049/jimmunol.0902941
发表时间: 2010-06-01
影响因子: 4.4
作者:
Connolly, Mary;Marrelli, Alessandra;Fearon, Ursula
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DOI: 10.4049/jimmunol.177.6.4072
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尖端:TLR2是急性阶段血清淀粉样蛋白A的功能受体。
DOI: 10.4049/jimmunol.181.1.22
发表时间: 2008-07-01
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Cheng N;He R;Tian J;Ye PP;Ye RD
通讯作者: Ye RD
DOI: 10.1016/s0002-9440(10)63631-0
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