Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats.
Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats.
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巨噬细胞 micro-RNA-155 促进脂多糖诱导的小鼠和大鼠急性肺损伤。
DOI：
10.1152/ajplung.00001.2016
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Yu Shi-Qiang
中科院分区：
文献类型：
--
作者：
Wang Wen;Liu Zhi;Su Jie;Chen Wen-Sheng;Wang Xiao-Wu;Bai San-Xing;Zhang Jin-Zhou;Yu Shi-Qiang
Micro-RNA（miR）-155是一种新型的基因调控因子，在炎症反应中具有重要作用。本研究旨在探讨miR-155在LPS诱导的急性肺损伤（ALI）中的作用。用LPS诱导小鼠急性肺损伤。对miR-155敲除小鼠进行的功能丧失实验表明，miR-155基因失活保护小鼠免受LPS诱导的ALI，与野生型对照相比，这表现为保留了肺通透性和减少了肺部炎症。骨髓移植实验鉴定了白细胞，但不是肺实质来源的miR-155促进的急性肺部炎症。Real-time PCR分析显示，LPS刺激后野生型小鼠肺组织中miR-155的表达显著升高。原位杂交显示miR-155主要表达于肺泡巨噬细胞。在分离的肺泡巨噬细胞和极化的骨髓来源的巨噬细胞中进行的体外实验证实，巨噬细胞中的miR-155表达响应于LPS刺激而增加。相反，肺泡巨噬细胞中的miR-155功能获得显著加重了LPS诱导的急性肺损伤。分子生物学研究发现，细胞因子信号传导的炎症抑制因子（SOCS-1）是miR-155的下游靶点。通过与SOCS-1 mRNA的3 '-UTR结合，miR-155下调SOCS-1表达，从而允许肺损伤期间的炎症反应。最后，我们产生了一种新的miR-155敲除大鼠品系，并表明miR-155的促炎作用在大鼠中是保守的。我们的研究证实miR-155是LPS刺激后的促炎因子，肺泡巨噬细胞来源的miR-155在LPS诱导的ALI中具有重要作用。
Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3'-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI.
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影响因子：
32.4
作者：
O'Connell RM;Kahn D;Gibson WS;Round JL;Scholz RL;Chaudhuri AA;Kahn ME;Rao DS;Baltimore D
通讯作者：
Baltimore D
影响因子：
3.1
作者：
Xie, Wenchao;Li, Ping;Mo, Yingxi
通讯作者：
Mo, Yingxi
影响因子：
3.7
作者：
Rouquette-Jazdanian AK;Kortum RL;Li W;Merrill RK;Nguyen PH;Samelson LE;Sommers CL
通讯作者：
Sommers CL
影响因子：
8
作者：
Varendi, Kart;Matlik, Kert;Andressoo, Jaan-Olle
通讯作者：
Andressoo, Jaan-Olle
影响因子：
37.8
作者：
Heymans, Stephane;Corsten, Maarten F.;Schroen, Blanche
通讯作者：
Schroen, Blanche