부산대학교 도서관

Airway epithelial cells respond to certain environmental stresses by mounting a proinflammatory response, which is characterized by enhanced synthesis and release of the neutrophil chemotactic and activating factor interleukin-8 (IL-8). IL-8 expression is regulated at the transcriptional level in part by the transcription factor nuclear factor (NF)-κB. We compared intracellular signaling mediating IL-8 gene expression in bronchial epithelial cells culturedin vitroand exposed to two inducers of cellular stress, sodium arsenite (AsIII), and vanadyl sulfate (VIV). Unstimulated bronchial epithelial cells expressed IL-8, and exposure to both metal compounds significantly enhanced IL-8 expression. Overexpression of a dominant negative inhibitor of NF-κB depressed both basal and metal-induced IL-8 expression. Low levels of nuclear NF-κB were constitutively present in unstimulated cultures. These levels were augmented by exposure to VIV, but not AsIII. Accordingly, VIVinduced IκBα breakdown and NF-κB nuclear translocation, whereas AsIIIdid not. However, both AsIIIand VIVenhanced κB-dependent transcription. In addition, AsIIIactivation of an IL-8 promoter-reporter construct was partially κB-dependent. These data suggested that AsIIIenhanced IL-8 gene transcription independently of IκB breakdown and nuclear translocation of NF-κB in part by enhancing transcription mediated by low levels of constitutive nuclear NF-κB.