Keratinocyte Growth Factor and Dexamethasone Treatments Protect Lung Epithelial Cells from Death by Oxidative Stress

The goal of this study was to determine whether keratinocyte growth factor (KGF) and dexamethasone (Dex) treatments, which induce peroxiredoxin 6 (Prdx6) production, can protect lung epithelial cells against oxidative stress. Prdx6 is an enzyme that has both phospholipase A 2 and peroxidase activities and can reduce peroxides, including lipid hydroperoxides, by a unique mechanism employing a single conserved cysteine. It is highly expressed in lung, both protecting against oxidative stress and regulating pulmonary surfactant phospholipid metabolism. A549 cells and primary cultures of rat lung alveolar type II cells were treated with 20 ng/ml KGF or 1 μM Dex or both and exposed to tert‐butyl hydroperoxide (tBOOH) or hydrogen peroxide (H 2 O 2 ) for 24 hours at several concentrations. Cell survival was assessed using the MTT or neutral red assays. For A549 cells and rat type II cells treated with tBOOH, the LD50 was about 150 μM while for A549 cells treated with H 2 O 2 it was 250 μM. Treatment with KGF or Dex alone protected cells substantially, while treatment with both KGF and Dex had an additive effect. Our studies show that KGF and Dex, which increase Prdx6 expression, can protect cells from oxidative stress and the combination is more protective than either treatment alone. Further study will be needed to determine whether Prdx6 is responsible for the observed protection in lung epithelial cells. Supported by HL P01‐75587.