| First Author | Zhang WJ | Year | 2011 |
| Journal | Free Radic Biol Med | Volume | 50 |
| Issue | 11 | Pages | 1517-25 |
| PubMed ID | 21376114 | Mgi Jnum | J:172087 |
| Mgi Id | MGI:5003408 | Doi | 10.1016/j.freeradbiomed.2011.02.027 |
| Citation | Zhang WJ, et al. (2011) Genetic ablation of phagocytic NADPH oxidase in mice limits TNFalpha-induced inflammation in the lungs but not other tissues. Free Radic Biol Med 50(11):1517-25 |
| abstractText | 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 TNFalpha-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 mug TNFalpha/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) TNFalpha-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-kappaB, and decreased gene expression of interleukin (IL)-1beta, IL-6, TNFalpha, 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 TNFalpha-induced, NF-kappaB-dependent acute inflammatory responses and tissue injury specifically in the lungs, which is effected by preferential leukocyte infiltration. |
