Modulation of endotoxin-induced NF-κB activation in lung and liver through TNF type 1 and IL-1 receptors

M. Audrey Koay, John W. Christman, L. James Wudel, Tara Allos, Dong Sheng Cheng, William C. Chapman, Timothy S. Blackwell

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19 Scopus citations


We investigated the requirement for tumor necrosis factor-α (TNF-α) and interleukin (IL)-1 receptors in the pathogenesis of the pulmonary and hepatic responses to Escherichia coli lipopolysaccharide (LPS) by studying wild-type mice and mice deficient in TNF type 1 receptor [TNFR1 knockout (KO)] or both TNF type 1 and IL-1 receptors (TNFR1/IL-1R KO). In lung tissue, NF-κB activation was similar among the groups after exposure to aerosolized LPS. After intraperitoneal injection of LPS, NF-κB activation in liver was attenuated in TNFR1 KO mice and further diminished in TNFR1/IL-1R KO mice; however, in lung tissue, no impairment in NF-κB activation was found in TNFR1 KO mice and only a modest decrease was found in TNFR1/IL-1R KO mice. Lung concentrations of KC and macrophage-inflammatory peptide 2 were lower in TNFR1 KO and TNFR1/IL-1R KO mice after aerosolized and intraperitoneal LPS. We conclude that LPS-induced NF-κB activation in liver is mediated through TNF-α- and IL-1 receptor-dependent pathways, but, in the lung, LPS-induced NF-κB activation is largely independent of these receptors.

Original languageEnglish
Pages (from-to)L1247-L1254
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6 27-6
StatePublished - Dec 1 2002


  • Chemokines
  • Cytokines
  • Macrophage
  • Neutrophil
  • Sepsis


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