Impaired pulmonary NF-kappaB activation in response to lipopolysaccharide in NADPH oxidase-deficient mice.
Reactive oxygen species (ROS) are thought to be involved in intracellular signaling, including activation of the transcription factor NF-kappaB. We investigated the role of NADPH oxidase in the NF-kappaB activation pathway by utilizing knockout mice (p47phox-/-) lacking the p47phox component of NADPH oxidase. Wild-type (WT) controls and p47phox-/- mice were treated with intraperitoneal (i.p.) Escherichia coli lipopolysaccharide (LPS) (5 or 20 microg/g of body weight). LPS-induced NF-kappaB binding activity and accumulation of RelA in nuclear protein extracts of lung tissue were markedly increased in WT compared to p47phox-/- mice 90 min after treatment with 20 but not 5 microg of i.p. LPS per g. In another model of lung inflammation, RelA nuclear translocation was reduced in p47phox-/- mice compared to WT mice following treatment with aerosolized LPS. In contrast to NF-kappaB activation in p47phox-/- mice, LPS-induced production of macrophage inflammatory protein 2 in the lungs and neutrophilic lung inflammation were not diminished in these mice compared to WT mice. We conclude that LPS-induced NF-kappaB activation is deficient in the lungs of p47phox-/- mice compared to WT mice, but this abnormality does not result in overt alteration in the acute inflammatory response.
Koay
M A
MA
Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 27232, USA.
Christman
J W
JW
Segal
B H
BH
Venkatakrishnan
A
A
Blackwell
T R
TR
Holland
S M
SM
Blackwell
T S
TS
D000818:Animals; D001692:Biological Transport; D002457:Cell Extracts; D002467:Cell Nucleus; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis; D004926:Escherichia coli; D005260:Female; D022781:Hepatocytes; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D051996:Transcription Factor RelA
D002457:Cell Extracts; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010750:Phosphoproteins; D051996:Transcription Factor RelA; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1