Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ.
Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ.
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炎症对于宿主防御是必不可少的，但如果不加以控制，可能导致组织损伤和器官衰竭。如何解决炎症仍然是难以捉摸的。在这里，我们报告，转录因子Miz 1是终止脂多糖（LPS）诱导的炎症所需的。Miz 1 POZ结构域的遗传破坏对其反式激活或抑制活性至关重要，导致LPS治疗小鼠的过度炎症，肺损伤和死亡率增加，同时降低铜绿假单胞菌肺炎小鼠的细菌负荷和死亡率。Miz 1 POZ结构域的缺失延长了促炎细胞因子的表达。在刺激后，Miz 1在Ser 178处磷酸化，这是募集组蛋白脱乙酰基酶1抑制C/EBP-δ转录所需的，C/EBP-δ是炎症放大器。我们的数据提供了一个长期寻求的机制，潜在的解决LPS诱导的炎症。
Inflammation is essential for host defense but can cause tissue damage and organ failure if unchecked. How the inflammation is resolved remains elusive. Here we report that the transcription factor Miz1 was required for terminating lipopolysaccharide (LPS)-induced inflammation. Genetic disruption of the Miz1 POZ domain, which is essential for its transactivation or repression activity, resulted in hyper-inflammation, lung injury and increased mortality in LPS-treated mice while reduced bacterial load and mortality in mice with Pseudomonas aeruginosa pneumonia. Loss of the Miz1 POZ domain prolonged pro-inflammatory cytokine expression. Upon stimulation, Miz1 was phosphorylated at Ser178, which is required for recruiting histone deacetylase 1 to repress transcription of C/EBP-δ, an amplifier of inflammation. Our data provide a long-sought mechanism underlying resolution of LPS-induced inflammation.
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DOI：
10.1073/pnas.1109285109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Kung, Vanderlene L.;Khare, Sonal;Hauser, Alan R.
通讯作者：
Hauser, Alan R.
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0906328106
发表时间：
2009-10-27
影响因子：
11.1
作者：
Liu, Jing;Zhao, Yingming;Lin, Anning
通讯作者：
Lin, Anning
影响因子：
64.5
作者：
Hsu, HL;Shu, HB;Goeddel, DV
通讯作者：
Goeddel, DV
影响因子：
5.3
作者：
Liu, J;Minemoto, Y;Lin, AN
通讯作者：
Lin, AN