Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis
Abstract
Acute bacterial inflammation is accompanied by excessive production of reactive oxygen and nitrogen species (ROS and RNS), which ultimately results in redox-stress, a leading pathogenic factor of the septic multiple organ dysfunction syndromes. According to the current paradigm, the inflammatory redox-stress is primarily attributed to the defense responses of the reticuloendothelial, endothelial, and lymphoepithelial components of tissue barriers to infections. Meanwhile, a large body of data accumulated in the last decade has pointed to an emerging role of ubiquitous mesenchymal stromal cells (MSCs) playing in the antibacterial and inflammatory events. In conjunction with this evidence, investigation of cellular pathways up-regulated in MSCs under redox stress conditions may provide new insights into mechanisms driving homeostatic responses of defense barriers to infections. This report presents results of in vitro investigations of the redox response of mouse MSCs to stimulation with Lipopolysaccharide (LPS) inflammagen. We have shown that MSCs treated with LPS experienced redox-stress due to induction of nitric oxide synthase (iNOS) and release of RNS and ROS. The compensatory response of MSCs to the LPS-induced cytotoxic stress was associated with activation of a number of the adaptive redox-response elements such as NFkB, Ref1, TRX1, Nrf2 and HO1, and autophagy, a cellular homeostatic process of remodeling and turnover of compromised cellular constituents. We propose that the cell survival mechanisms activated in LPS-treated MSCs in vitro could be a part of adaptive responses employed by stromal cells under septic conditions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 08, 2013
- Accession Number
- ADA575730
Entities
People
- Bradley R. Garrison
- Dennis P. Mcdaniel
- Dilber Nurmemet
- Juliann G Kiang
- Min Zhai
- Nikolai V. Gorbunov
- Pei-jyun Liao
Organizations
- Armed Forces Radiobiology Research Institute