Multiorgan nuclear factor kappa B activation in a transgenic mouse model of systemic inflammation

Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1095-101. doi: 10.1164/ajrccm.162.3.9906129.


We utilized a line of transgenic mice expressing Photinus luciferase complementary DNA (cDNA) under the control of a nuclear factor kappa B (NF-kappaB)-dependent promoter (from the 5' human immunodeficiency virus-1 [HIV-1] long terminal repeat) to examine the role of NF-kappaB activation in the pathogenesis of systemic inflammation induced by bacterial endotoxin (lipopolysaccharide [LPS]). After intraperitoneal injection of E. coli LPS, these mice displayed a time- and dose-dependent, organ-specific pattern of luciferase expression, showing that NF-kappaB-dependent gene transcription is transiently activated in multiple organs by systemic LPS administration. Luciferase expression in liver could be specifically blocked by intravenous administration of replication-deficient adenoviral vectors expressing a dominant inhibitor of NF-kappaB (IkappaB-alphaDN), confirming that luciferase gene expression is a surrogate marker for NF-kappaB activation in this line of mice. After treatment with intraperitoneal LPS, the mice were found to have increased lung tissue messenger RNA (mRNA) expression of a variety of cytokines that are thought to be NF-kappaB-dependent, as well as elevated serum concentrations of presumed NF-kappaB-dependent cytokines. In lung tissue homogenates, a close correlation was identified between luciferase activity and KC levels. These studies show that systemic treatment with LPS orchestrates a multiorgan NF-kappaB-dependent response that likely regulates the pathobiology of systemic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA, Complementary / genetics
  • HIV Enhancer / genetics*
  • Humans
  • Lipopolysaccharides / immunology
  • Luciferases / genetics
  • Lung / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • RNA, Messenger / genetics
  • Systemic Inflammatory Response Syndrome / genetics*
  • Systemic Inflammatory Response Syndrome / immunology


  • Cytokines
  • DNA, Complementary
  • Lipopolysaccharides
  • RNA, Messenger
  • Luciferases