title: 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 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.
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-1402, USA. nikolaiv.gorbunov@gmail.com
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Gorbunov
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Garrison
authors.forename: Dennis P
authors.initials: DP
authors.lastname: McDaniel
authors.forename: Min
authors.initials: M
authors.lastname: Zhai
authors.forename: Pei-Jyun
authors.initials: PJ
authors.lastname: Liao
authors.forename: Dilber
authors.initials: D
authors.lastname: Nurmemet
authors.forename: Juliann G
authors.initials: JG
authors.lastname: Kiang
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D018805:Sepsis / Q000378:metabolism / Q000473:pathology*; D013879:Thioredoxins / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D013879:Thioredoxins; D052247:Nitric Oxide Synthase Type II