Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses.
Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses.
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DOI：
10.1084/jem.20090560
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发表时间：
2009-08-31
期刊：
影响因子：
--
通讯作者：
Kishimoto T
中科院分区：
文献类型：
--
作者：
Kimura A;Naka T;Nakahama T;Chinen I;Masuda K;Nohara K;Fujii-Kuriyama Y;Kishimoto T
Toll样受体（TLR）信号在针对病原体的先天免疫应答中起着至关重要的作用。在这项研究中，我们发现芳烃受体（Ahr）负性调节巨噬细胞内脂多糖（LPS）介导的炎症反应。在LPS刺激的巨噬细胞中可诱导Ahr，而转化生长因子（TGF）-β和白细胞介素（IL）-6可诱导幼稚T细胞中的Ahr。与野生型（WT）细胞相比，Ahr缺陷型巨噬细胞产生的IL-6和肿瘤坏死因子（TNF）-α显著增加。Ahr缺陷小鼠对LPS诱导的致死性休克比WT小鼠更敏感。信号转导和转录激活因子1（Stat 1）缺陷，以及Ahr缺陷，增强LPS诱导的IL-6的产生。我们发现在LPS刺激的巨噬细胞中，Ahr与Stat 1和核因子-κ B（NF-κB）形成复合物，从而导致IL-6启动子活性的抑制。因此，Ahr通过与Stat 1相互作用在LPS信号通路的负调控中起着重要作用。
Toll-like receptor (TLR) signals perform a crucial role in innate immune responses to pathogens. In this study, we found that the aryl hydrocarbon receptor (Ahr) negatively regulates inflammatory responses mediated by lipopolysaccharide (LPS) in macrophages. Ahr was induced in macrophages stimulated by LPS, but not by transforming growth factor (TGF)-β plus interleukin (IL)-6, which can induce Ahr in naive T cells. The production of IL-6 and tumor necrosis factor (TNF)-α by LPS was significantly elevated in Ahr-deficient macrophages compared with that in wild-type (WT) cells. Ahr-deficient mice were more highly sensitive to LPS-induced lethal shock than WT mice. Signal transducer and activator of transcription 1 (Stat1) deficiency, as well as Ahr deficiency, augmented LPS-induced IL-6 production. We found that Ahr forms a complex with Stat1 and nuclear factor-kappa B (NF-κB) in macrophages stimulated by LPS, which leads to inhibition of the promoter activity of IL-6. Ahr thus plays an essential role in the negative regulation of the LPS signaling pathway through interaction with Stat1.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
抑制白介素1受体/TOLL样受体信号传导通过剪接的短形式的MyD88抑制是由于其未能募集IRAK-4所致。
影响因子：
15.3
作者：
Burns, K;Janssens, S;Brissoni, B;Olivos, N;Beyaert, R;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
4.1
作者：
Kanno, Yuichiro;Takane, Yusuke;Inouye, Yoshio
通讯作者：
Inouye, Yoshio
DOI：
10.1073/pnas.90.6.2532
发表时间：
1993-03-15
影响因子：
11.1
作者：
BROWN, K;PARK, S;SIEBENLIST, U
通讯作者：
SIEBENLIST, U
影响因子：
4.8
作者：
Naiki, Y;Michelsent, KS;Arditi, M
通讯作者：
Arditi, M