Hepatic expression of multiple acute phase proteins and down-regulation of nuclear receptors after acute endotoxin exposure

Biochem Pharmacol. 2004 Apr 1;67(7):1389-97. doi: 10.1016/j.bcp.2003.12.012.


Acute systemic lipopolysaccharide (endotoxin, LPS) exposure, which can lead to septic shock, enhances the hepatic expression of inflammatory and acute-phase proteins (APPs). To better understand how LPS aggravates damage, changes in hepatic gene expression after a single LPS dose was screened by using microarrays for 1176 rat genes. We detected more than 20 new potential LPS-induced APPs. Following acute LPS challenge, significant up-regulation of the steady-state mRNA levels of several important early transcription factors, such as c-jun and STAT3, and cytokine-associated genes, was observed. In contrast, RT-PCR analysis revealed marked down-regulation of the nuclear receptors RXRalpha, PXR, FXR, LXR, PPARalpha and CAR. Also genes encoding lipolytic, antioxidant as well as drug- and alcohol-metabolizing enzymes were down-regulated. These data suggest that acute LPS treatment induces important early transcription factors and co-ordinately down-regulates nuclear receptors, and that this results in altered expression of a large number of downstream genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Animals
  • Down-Regulation / drug effects
  • Endotoxins / pharmacology*
  • Gene Expression / drug effects*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Polymerase Chain Reaction
  • Rats
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*


  • Acute-Phase Proteins
  • Endotoxins
  • Receptors, Cytoplasmic and Nuclear