Modulation of endotoxin-induced NF-kappa B activation in lung and liver through TNF type 1 and IL-1 receptors.
We investigated the requirement for tumor necrosis factor-alpha (TNF-alpha) 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-kappaB activation was similar among the groups after exposure to aerosolized LPS. After intraperitoneal injection of LPS, NF-kappaB 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-kappaB 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-kappaB activation in liver is mediated through TNF-alpha- and IL-1 receptor-dependent pathways, but, in the lung, LPS-induced NF-kappaB activation is largely independent of these receptors.
Koay
M Audrey
MA
Departments of Medicine and Surgery, Vanderbilt University School of Medicine, Nashville , Tennessee 37232-2650, USA.
Christman
John W
JW
Wudel
L James
LJ
Allos
Tara
T
Cheng
Dong-Sheng
DS
Chapman
William C
WC
Blackwell
Timothy S
TS
D000336:Aerosols; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology*; D011014:Pneumonia / Q000139:chemically induced; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I
D000336:Aerosols; D015703:Antigens, CD; D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I