Exposure of Monocytic Cells to Lipopolysaccharide Induces Coordinated Endotoxin Tolerance, Mitochondrial Biogenesis, Mitophagy, and Antioxidant Defenses.

TitleExposure of Monocytic Cells to Lipopolysaccharide Induces Coordinated Endotoxin Tolerance, Mitochondrial Biogenesis, Mitophagy, and Antioxidant Defenses.
Publication TypeJournal Article
Year of Publication2018
AuthorsWiddrington, JD, Gomez-Duran, A, Pyle, A, Ruchaud-Sparagano, M-H, Scott, J, Baudouin, SV, Rostron, AJ, Lovat, PE, Chinnery, PF, A Simpson, J
JournalFront Immunol
Volume9
Pagination2217
Date Published2018
ISSN1664-3224
Abstract

In order to limit the adverse effects of excessive inflammation, anti-inflammatory responses are stimulated at an early stage of an infection, but during sepsis these can lead to deactivation of immune cells including monocytes. In addition, there is emerging evidence that the up-regulation of mitochondrial quality control mechanisms, including mitochondrial biogenesis and mitophagy, is important during the recovery from sepsis and inflammation. We aimed to describe the relationship between the compensatory immune and mitochondrial responses that are triggered following exposure to an inflammatory stimulus in human monocytic cells. Incubation with lipopolysaccharide resulted in a change in the immune phenotype of THP-1 cells consistent with the induction of endotoxin tolerance, similar to that seen in deactivated septic monocytes. After exposure to LPS there was also early evidence of oxidative stress, which resolved in association with the induction of antioxidant defenses and the stimulation of mitochondrial degradation through mitophagy. This was compensated by a parallel up-regulation of mitochondrial biogenesis that resulted in an overall increase in mitochondrial respiratory activity. These observations improve our understanding of the normal homeostatic responses that limit the adverse cellular effects of unregulated inflammation, and which may become ineffective when an infection causes sepsis.

DOI10.3389/fimmu.2018.02217
Alternate JournalFront Immunol
Citation Key10.3389/fimmu.2018.02217
PubMed ID30319656
PubMed Central IDPMC6170658
Grant List / / Wellcome Trust / United Kingdom
MC_UP_1501/2 / / Medical Research Council / United Kingdom