Endotoxin regulates matrix genes increasing reactive oxygen species generation by intercellular communication between palmitate-treated hepatocyte and stellate cell

Waleska Dornas, Denise Glaise, Aude Bodin, Ahmad Sharanek, Audrey Burban, Dounia Le Guillou, Sacha Robert, Stephanie Dutertre, Caroline Aninat, Anne Corlu, Vincent Lagente

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Previous studies have shown that gut-derived bacterial endotoxins contribute in the progression of simple steatosis to steatohepatitis, although the mechanism(s) remains inaccurate to date. As hepatic stellate cells (HSC) play a pivotal role in the accumulation of excessive extracellular matrix (ECM), leading to collagen deposition, fibrosis, and perpetuation of inflammatory response, an in vitro model was developed to investigate the crosstalk between HSC and hepatocytes (human hepatoma cell) pretreated with palmitate. Bacterial lipopolysaccharide (LPS) stimulated HSC with phosphorylation of the p38 mitogen-activated protein kinase/NF-κB pathway, while several important pro-inflammatory cytokines were upregulated in the presence of hepatocyte–HSC. Concurrently, fibrosis-related genes were regulated by palmitate and the inflammatory effect of endotoxin where cells were more exposed or sensitive to reactive oxygen species (ROS). This interaction was accompanied by increased expression of the mitochondrial master regulator, proliferator-activated receptor gamma coactivator alpha, and a cytoprotective effect of the agent N-acetylcysteine suppressing ROS production, transforming growth factor-β1, and tissue inhibitor of metalloproteinase-1. In summary, our results demonstrate that pro-inflammatory mediators LPS-induced promote ECM rearrangement in hepatic cells transcriptionally committed to the regulation of genes encoding enzymes for fatty acid metabolism in light of differences that might require an alternative therapeutic approach targeting ROS regulation.

Original languageEnglish (US)
Pages (from-to)122-133
Number of pages12
JournalJournal of cellular physiology
Volume234
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • hepatic stellate cells (HSC)
  • inflammation
  • lipopolysaccharide (LPS)
  • nonalcoholic steatohepatitis (NASH)

Fingerprint Dive into the research topics of 'Endotoxin regulates matrix genes increasing reactive oxygen species generation by intercellular communication between palmitate-treated hepatocyte and stellate cell'. Together they form a unique fingerprint.

  • Cite this