Impaired pulmonary NF-kappa B activation in response to lipopolysaccharidein NADPH oxidase-deficient mice

Reactive oxygen species (ROS) are thought to be involved in intracellular s ignaling, including activation of the transcription factor NF-kappaB. We in vestigated the role of NADPH oxidase in the NF-KB activation pathway by uti lizing knockout mice (p47(phox-/-)) lacking the p47(phox) component of NADP H oxidase. Wild-type (WT) controls and P47(phox-/-) mice were treated with intraperitoneal (i.p.) Escherichia coli lipopolysaccharide (LPS) (5 or 20 m ug/g of body weight). LPS-induced NF-kappaB binding activity and accumulati on of RelA in nuclear protein extracts of lung tissue were markedly increas ed in WT compared to p47(phox-/-) mice 90 min after treatment with 20 but n ot 5 mug of i.p. LPS per g. In another model of lung inflammation, RelA nuc lear translocation was reduced in p47(phox-/-) mice compared to. WT mice fo llowing treatment with aerosolized LPS. In contrast to NF-kappaB activation in p47(phox-/-) mice, LPS-induced production of macrophage inflammatory pr otein 2 in the lungs and neutrophilic lung inflammation were not diminished in these mice compared to WT mice. We conclude that LPS-induced NF-KB acti vation is deficient in the lungs of p47(phox-/-) mice compared to WT mice, but this abnormality does not result in overt alteration in the acute infla mmatory response.