Induction of tumor necrosis factor alpha and interleukin-8 gene expressionin bronchial epithelial cells by toxic shock syndrome toxin 1

Major histocompatibility complex (MHC) class II engagement by toxic shock s yndrome toxin 1 (TSST-1) transduces signals leading to proinflammatory cyto kine gene expression (tumor necrosis factor alpha [TNF-alpha]) in human mon ocytes. To study the proinflammatory role of MHC class II molecules express ed by bronchial epithelial cells (BEC), primary human BEC were isolated ti- om surgical bronchial samples, expanded in vitro, and cultured in the prese nce or absence of gamma interferon (IFN-gamma) for 48 h, I-125-TSST-1 bindi ng to BEC pretreated with IFN-gamma was inhibited up to 97% by anti-MHC cla ss II monoclonal antibody 3B12, indicating that in BEC also MHC class II mo lecules were targets for the staphylococcal exotoxin. As analyzed by a quan titative reverse transcriptase PCR, a 1-h stimulation of BEC with TSST-1 re sulted 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 t ime course study, peak expression of TNF-alpha and IL-8 mRNA was reached 6 h after TSST-1 stimulation. These results demonstrate that bacterial supera ntigen 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 cont ributing to the perpetuation of bronchial mucosa inflammation via chemokine or cytokine gene expression.