CD14-dependent alterations in c-Jun expression in the liver after burn injury

J Surg Res. 2004 Nov;122(1):36-42. doi: 10.1016/j.jss.2004.07.007.

Abstract

Background: Burn injury-triggered activation of lipopolysaccharide signaling via the CD14 pathway alters the expression of a variety of downstream genes contributing to pathogenic changes in distant organs. The regulation of CD14 and its role in the immediate-early response of c-Jun in the liver after burn injury were investigated in this study.

Materials and methods: An incidental identification of the differential induction of CD14 mRNA after an approximately 18% TBSA burn injury in mice was confirmed by RT-PCR and immunohistochemical analyses of CD14 expression. Subsequently, CD14's role in the immediate-early regulation of c-Jun expression in the liver after injury was examined by Western blot analysis using CD14 knockout (KO) mice.

Results: RT-PCR analysis demonstrated a rapid and transient induction of CD14 mRNA in the liver and lungs of mice after injury. Immunohistochemical analysis revealed a peak induction of CD14 reactivity in cells appearing to be Kupffer cells at day 1 after injury. Furthermore, an augmented and delayed induction of c-Jun mRNA was observed in the liver of CD14 KO mice after injury compared to wild-type controls. The induction of phosphorylated (serine 63 or serine 73) forms of c-Jun after injury was lower in the livers of CD14 KO mice than that in WT controls.

Conclusions: This study provides evidence that injury elicits CD14 induction as well as hyperphosphorylation of the c-Jun N-terminus activation domain and that CD14 is involved in the modulation of c-Jun's transactivation potential via phosphorylation, which may be associated with hepatic pathogenesis after injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burns / metabolism*
  • Female
  • Kupffer Cells / metabolism
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / metabolism*
  • Liver / metabolism*
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism

Substances

  • Lipopolysaccharide Receptors
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger