Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis.
Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis.
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DOI：
10.1155/2013/186795
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发表时间：
2013
影响因子：
--
通讯作者：
Kiang JG
中科院分区：
文献类型：
--
作者：
Gorbunov NV;Garrison BR;McDaniel DP;Zhai M;Liao PJ;Nurmemet D;Kiang JG
急性细菌性炎症伴随着细菌毒素的过度释放和活性氧和氮物质（ROS和RNS）的产生，其最终导致氧化还原应激。这些因素可诱导组织屏障组分的损伤，包括对普遍存在的间充质基质细胞（MSC）的损伤，并因此可加重脓毒性多器官功能障碍。MSC为了在这些应激条件下生存而采用的机制仍然知之甚少，需要澄清。在这份报告中，我们证明，在体外处理的MSC与脂多糖（LPS）诱导的炎症反应，其中包括，但不限于，上调诱导型一氧化氮合酶和RNS和活性氧的释放。这些事件在MSC中触发了一系列反应，驱动适应性重塑和对“自我造成的”氧化应激的抵抗。因此，虽然MSC显示出高水平的组成型存在的适应原，例如，HSP 70和线粒体Sirt3，但用LPS处理诱导了许多适应性反应，包括氧化还原反应元件如NFkB、TRX1、Ref 1、Nrf2、FoxO3a、HO 1的诱导和核转位，以及自噬和线粒体重塑的激活。我们认为，上述促生存途径在体外激活的骨髓间充质干细胞可能是一个适应性反应的一部分，在脓毒症条件下基质细胞。
Acute bacterial inflammation is accompanied by excessive release of bacterial toxins and production of reactive oxygen and nitrogen species (ROS and RNS), which ultimately results in redox stress. These factors can induce damage to components of tissue barriers, including damage to ubiquitous mesenchymal stromal cells (MSCs), and thus can exacerbate the septic multiple organ dysfunctions. The mechanisms employed by MSCs in order to survive these stress conditions are still poorly understood and require clarification. In this report, we demonstrated that in vitro treatment of MSCs with lipopolysaccharide (LPS) induced inflammatory responses, which included, but not limited to, upregulation of iNOS and release of RNS and ROS. These events triggered in MSCs a cascade of responses driving adaptive remodeling and resistance to a “self-inflicted” oxidative stress. Thus, while MSCs displayed high levels of constitutively present adaptogens, for example, HSP70 and mitochondrial Sirt3, treatment with LPS induced a number of adaptive responses that included induction and nuclear translocation of redox response elements such as NFkB, TRX1, Ref1, Nrf2, FoxO3a, HO1, and activation of autophagy and mitochondrial remodeling. We propose that the above prosurvival pathways activated in MSCs in vitro could be a part of adaptive responses employed by stromal cells under septic conditions.
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影响因子：
7.4
作者：
Gill, Roop;Tsung, Allan;Billiar, Timothy
通讯作者：
Billiar, Timothy
影响因子：
4.3
作者：
Iyer SS;Torres-Gonzalez E;Neujahr DC;Kwon M;Brigham KL;Jones DP;Mora AL;Rojas M
通讯作者：
Rojas M
DOI：
10.1073/pnas.1014156108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Fujita, Ken-ichi;Maeda, Daisuke;Srinivasula, Srinivasa M.
通讯作者：
Srinivasula, Srinivasa M.
影响因子：
64.5
作者：
Imai Y;Kuba K;Neely GG;Yaghubian-Malhami R;Perkmann T;van Loo G;Ermolaeva M;Veldhuizen R;Leung YH;Wang H;Liu H;Sun Y;Pasparakis M;Kopf M;Mech C;Bavari S;Peiris JS;Slutsky AS;Akira S;Hultqvist M;Holmdahl R;Nicholls J;Jiang C;Binder CJ;Penninger JM
通讯作者：
Penninger JM
影响因子：
3.4
作者：
Kiang, Juliann G.;Jiao, Wan;Cary, Lynnette H.;Mog, Steven R.;Elliott, Thomas B.;Pellmar, Terry C.;Ledney, G. David
通讯作者：
Ledney, G. David