Impaired pulmonary NF-kappaB activation in response to lipopolysaccharide in NADPH oxidase-deficient mice.

Koay MA, Christman JW, Segal BH, Venkatakrishnan A, Blackwell TR, Holland SM, Blackwell TS
Infect Immun. 2001 69 (10): 5991-6

PMID: 11553535 · PMCID: PMC98726 · DOI:10.1128/IAI.69.10.5991-5996.2001

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.

MeSH Terms (23)

Animals Biological Transport Cell Extracts Cell Nucleus Chemokine CXCL2 Chemokines Chemokines, CXC Escherichia coli Female Hepatocytes Injections, Intraperitoneal Lipopolysaccharides Liver Lung Male Mice Mice, Inbred C57BL Mice, Knockout NADPH Oxidases Neutrophils NF-kappa B Phosphoproteins Transcription Factor RelA

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