Reactive oxygen intermediates stimulate interleukin-6 production in human bronchial epithelial cells

Reactive oxygen intermediates (ROIs) play an important role in the initiati on and progression of lung diseases. In this study, we investigated whether ROIs were involved in the induction of interleukin (IL)-6 in human bronchi al epithelial cells. We exposed normal human bronchial epithelial cells as well as a human bronchial epithelial cell line, HS-24, to ROIs. We measured the amount of IL-6 in the culture supernatants using ELISA and the IL-6 mR NA levels using RT-PCR. Superoxide anions (O-2(-)), but not hydrogen peroxi de (H2O2), increased IL-6 production. To examine whether it is a cell type- specific mechanism of airway epithelial cells, the experiments were also pe rformed in human lung fibroblasts, WI-38-40. In WI-38-40 cells, neither O-2 (-) nor H2O2 increased IL-6 production. In contrast, tumor necrosis factor (TNF)-alpha (200 U/ml) induced IL-6 at the protein and mRNA levels in both airway epithelial cells and lung fibroblasts. This cytokine-induced IL-6 pr oduction was significantly suppressed by several antioxidants, including di methyl sulfoxide (DMSO), in airway epithelial cells. In WI-38-40 cells, DMS O was not able to suppress IL-6 production induced by TNF-alpha. Pretreatme nt with DMSO recovered the TNF-ol-induced depletion of intracellular reduce d glutathione in HS-24 cells. These findings indicate that oxidant stress s pecifically induces IL-6 production in human bronchial epithelial cells and that in these cells ROIs may be involved in IL-6 production after stimulat ion with cytokines such as TNF-alpha. Presumably, ROIs participate in the l ocal immune response in lung diseases via IL-6 release from bronchial epith elial cells.