miR-15a/16 regulates macrophage phagocytosis after bacterial infection.
miR-15a/16 regulates macrophage phagocytosis after bacterial infection.
复制标题
miR-15a/16调节细菌感染后巨噬细胞吞噬作用。
DOI：
10.4049/jimmunol.1401372
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发表时间：
2014-11-01
期刊：
影响因子：
--
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Moon HG;Yang J;Zheng Y;Jin Y
Bacterial infection and its associated sepsis are devastating clinical entities which lead to high mortality and morbidity in critically ill patients. Phagocytosis, along with other innate immune responses, exerts crucial impacts on the outcomes of these patients. MicroRNAs (miRNAs) are a novel class of regulatory noncoding RNAs targeting specific mRNAs for modulation of translation and expression of a targeted protein. The roles of miRNAs in host defense against bacterial sepsis remain unclear. We found that bacterial infections and/or bacterial-derived LPS enhanced the level of miR-15a/16 in bone marrow derived macrophages (BMDMs). Deletion of miR-15a/16 (miR-15a/16-/-) in myeloid cells significantly decreased the bacterial infection associated mortality in sepsis mouse models. Moreover, miR-15a/16 deficiency (miR-15a/16-/-) resulted in augmented phagocytosis and generation of mitochondrial reactive oxygen species (ROS) in BMDMs. Supportively, over-expression of miR-15a/16 using miRNA mimics led to decreased phagocytosis and decreased generation of mitochondrial ROS. Mechanistically, deletion of miR-15a/16 up-regulated the expression of toll-like receptor 4 (TLR4) via targeting the principle transcriptional regulator PU.1 locating on the promoter region of TLR4, and further modulated TLR4's downstream signaling molecules, including Rho GTPase Cdc 42 and TRAF6. Additionally, deficiency of miR-15a/16 also facilitated TLR4-mediated pro-inflammatory cytokine/chemokine release from BMDMs at the initial phase of infections. Taken together, miR-15a/16 altered phagocytosis and bacterial clearance by targeting, at least partially, on the TLR4-associated pathways, subsequently affecting the survival of septic mice.
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DOI：
10.1084/jem.20031237
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Doyle SE;O'Connell RM;Miranda GA;Vaidya SA;Chow EK;Liu PT;Suzuki S;Suzuki N;Modlin RL;Yeh WC;Lane TF;Cheng G
通讯作者：
Cheng G
DOI：
10.1038/nri3151
发表时间：
2012-02-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Jennewein, Carla;von Knethen, Andreas;Bruene, Bernhard
通讯作者：
Bruene, Bernhard
影响因子：
3.1
作者：
McClure, Clara;Brudecki, Laura;El Gazzar, Mohamed
通讯作者：
El Gazzar, Mohamed
影响因子：
7.8
作者：
Mohammadi, Sina;Isberg, Ralph R.
通讯作者：
Isberg, Ralph R.