Superoxide dismutase attenuates hyperoxia-induced interleukin-8 induction via AP-1.
Exposure of lung epithelial cells to hyperoxia results in the generation of excess reactive oxygen species (ROS), cell damage, and production of proinflammatory cytokines (interleukin-8; IL-8). Although activation of the NF-kappaB and c-Jun N-terminal kinase (JNK)/activator protein (AP)-1 transcription pathways occurs in hyperoxia, it is unclear whether activation of the AP-1 pathway has a direct impact on IL-8 production and whether overexpression of superoxide dismutase (SOD) can mitigate these proinflammatory processes. A549 cells were exposed to 95% O(2), and ROS production, AP-1 activation, and IL-8 levels were determined. Experimental groups included cells transduced with a recombinant adenovirus encoding CuZnSOD or MnSOD (two- to threefold increased activity) or transfected with a JNK1 small interfering RNA (RNAi). Hyperoxia resulted in significant increases in ROS generation, AP-1 activation, and IL-8 production, which were significantly attenuated by overexpression of either MnSOD or CuZnSOD. JNK1 RNAi also moderated IL-8 induction. The data indicate that activation of JNK1/AP-1 and subsequent IL-8 induction in hyperoxia are mediated by intracellular ROS, with SOD having significant protective effects.
Joseph
Ansamma
A
CardioPulmonary Research Institute, Department of Medicine, Winthrop University Hospital, State University of New York Stony Brook School of Medicine, Mineola, NY 11501, USA.
Li
Yuchi
Y
Koo
Hshi-Chi
HC
Davis
Jonathan M
JM
Pollack
Simcha
S
Kazzaz
Jeffrey A
JA
D015153:Blotting, Western; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection
D016209:Interleukin-8; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D013482:Superoxide Dismutase