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Free Radic Biol Med. 2011 Jun 1;50(11):1517-25. doi: 10.1016/j.freeradbiomed.2011.02.027. Epub 2011 Mar 2.

Genetic ablation of phagocytic NADPH oxidase in mice limits TNFα-induced inflammation in the lungs but not other tissues.

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  • 1Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. weijian.zhang@oregonstate.edu

Abstract

In vitro and limited in vivo evidence suggests that reactive oxygen species derived from NADPH oxidases (NOX-ROS) play an important role in inflammatory responses by enhancing the activity of redox-sensitive cell signaling pathways and transcription factors. Here, we investigated the role of NOX-ROS in TNFα-induced acute inflammatory responses in vivo, using mice deficient in the gp91(phox) (NOX2) or p47(phox) subunits of NADPH oxidase. Age- and body weight-matched C57BL/6J wild-type (WT) and gp91(phox) or p47(phox) knockout mice were injected intraperitoneally with 50 μg TNFα/kg bw or saline vehicle control and sacrificed at various time points up to 24 h. Compared to WT mice, gp91(phox -/-) mice exhibited significantly diminished (P<0.05) TNFα-induced acute inflammatory responses in the lungs but not other tissues, including heart, liver, and kidney, as evidenced by decreased activation of the redox-sensitive transcription factor NF-κB, and decreased gene expression of interleukin (IL)-1β, IL-6, TNFα, E-selectin, and other cellular adhesion molecules. Similar results were observed in p47(phox -/-) mice. Interestingly, decreased lung inflammation in knockout mice was accompanied by increased leukocyte infiltration into the lungs compared to other tissues. Our data suggest that phagocytic NOX-ROS signaling plays a critical role in promoting TNFα-induced, NF-κB-dependent acute inflammatory responses and tissue injury specifically in the lungs, which is effected by preferential leukocyte infiltration.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21376114
[PubMed - indexed for MEDLINE]
PMCID:
PMC3090478
Free PMC Article

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