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Induction of tumor necrosis factor alpha and interleukin-8 gene expression in bronchial epithelial cells by toxic shock syndrome toxin 1.
Infection and Immunity
Major histocompatibility complex (MHC) class II engagement by toxic shock syndrome toxin 1 (TSST-1) transduces signals leading to proinflammatory cytokine gene expression (tumor necrosis factor alpha [TNF-alpha]) in human monocytes. To study the proinflammatory role of MHC class II molecules expressed by bronchial epithelial cells (BEC), primary human BEC were isolated from surgical bronchial samples, expanded in vitro, and cultured in the presence or absence of gamma interferon (IFN-gamma) for 48 h. (125)I-TSST-1 binding to BEC pretreated with IFN-gamma was inhibited up to 97% by anti-MHC class II monoclonal antibody 3B12, indicating that in BEC also MHC class II molecules were targets for the staphylococcal exotoxin. As analyzed by a quantitative reverse transcriptase PCR, a 1-h stimulation of BEC with TSST-1 resulted in a vigorous expression of TNF-alpha and interleukin-8 (IL-8) genes. TNF-alpha and IL-8 expression was optimal in BEC pretreated with 50 IU of IFN-gamma/ml, whereas TSST-1 stimulation of BEC pretreated with 200 IU of IFN-gamma/ml failed to enhance either TNF-alpha or IL-8 transcripts. In a time course study, peak expression of TNF-alpha and IL-8 mRNA was reached 6 h after TSST-1 stimulation. These results demonstrate that bacterial superantigen TSST-1 binds to MHC molecules on BEC and induces TNF-alpha and IL-8 gene expression upon engagement of MHC class II molecules on BEC, thus contributing to the perpetuation of bronchial mucosa inflammation via chemokine or cytokine gene expression.
Antigen-Presenting Cells, Bacterial Toxins, Bronchi, Cells, Cultured, Enterotoxins, Epithelial Cells, Gene Expression, HLA-DR Antigens, Histocompatibility Antigens Class II, Humans, Inflammation, Interleukin-8, RNA, Messenger, Signal Transduction, Superantigens, Tumor Necrosis Factor-alpha
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