Effect of Cigarette Smoke on the Activation of Transcription Factors in Mouse Lung

Abstract

The effect of cigarette smoke on in vitro and in vivo transcription factor activation in the lung was examined. We first examined if NF-κB is activated by cigarette smoke condensate (CSC) in vitro. Using two different lung cell lines (H1299 and H-838), we did not observe activation of NF-κB following CSC exposure. We next examined if cigarette smoke could activate NF-κB in vivo. Mice were exposed to cigarette smoke for 1, 2, 3, or 6 hr, and 2, 5, 10, 15, 20, 42, or 56 days (6 hr/day, 5 days/wk). For all times except 20 and 42 days, the DNA binding activity of NF-κB in the lung and liver was either not changed or decreased by exposure to cigarette smoke. For the 20- and 42-day time points, the DNA binding activity in the lung was slightly increased. We also examined two other transcription factors: AP-1 and hypoxia inducible factor (HIF). Similar to NF-κB, the DNA binding activity of AP-1 and HIF was slightly elevated at 42 days but decreased at 56 days. These studies show that cigarette smoke does not activate NF-κB, AP-1 or HIF in the lung. Cigarette smoke activation of other transcription factors in the lung is currently being studied. (Supported by Kentucky Lung Cancer Research Program)