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Oxidative Medicine and Cellular Longevity
Volume 2013 (2013), Article ID 186795, 16 pages
http://dx.doi.org/10.1155/2013/186795
Research Article

Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis

1Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-1402, USA
2Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
3Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
4Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA

Received 23 December 2012; Revised 8 March 2013; Accepted 11 March 2013

Academic Editor: Sumitra Miriyala

Copyright © 2013 Nikolai V. Gorbunov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.