Status of bacterial colonization, Toll-like receptor expression and nuclear factor-kappa B activation in normal and diseased human livers

Clin Immunol. 2011 Jan;138(1):41-9. doi: 10.1016/j.clim.2010.09.006. Epub 2010 Oct 12.

Abstract

Epidemiological data on bacterial translocation (BT), colonization and inflammation in normal human livers is lacking. In this study we investigated the status of bacterial colonization and inflammation in the normal, cirrhotic primary biliary cirrhosis (PBC), and nonalcoholic steatohepatitis (NASH) human liver tissues. Comparatively normal livers showed increased bacterial colonization than PBC and NASH. We analyzed mRNA levels of Toll-like receptors (TLR) 2 and TLR4, and protein levels of TLR4. Phosphorylated IKKα (pIKKα) protein estimation served as a marker for nuclear factor-kappa B (NF-κB) activation. In spite of the increased bacterial colonization in normal liver tissues, lower levels of TLR2/4 mRNA and TLR4 and pIKKα proteins were found compared to PBC and NASH indicating the maintenance of suppressed inflammation and immune tolerance in normal livers. To our knowledge, this is the first clinical evidence showing suppressed inflammation despite bacterial colonization in normal human livers thus maintaining liver immune homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria, Aerobic / isolation & purification*
  • Fatty Liver / metabolism
  • Fatty Liver / microbiology
  • Female
  • Gene Expression / genetics
  • Gram-Positive Bacteria / isolation & purification
  • Humans
  • I-kappa B Kinase / metabolism
  • Liver / metabolism*
  • Liver / microbiology*
  • Liver Cirrhosis, Biliary / metabolism
  • Liver Cirrhosis, Biliary / microbiology
  • Liver Diseases / metabolism*
  • Liver Diseases / microbiology*
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Non-alcoholic Fatty Liver Disease
  • Phosphorylation
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*

Substances

  • NF-kappa B
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • I-kappa B Kinase