1. Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4
- Author
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Devaney, James M., Greene, Catherine M., Taggart, Clifford C., Carroll, Tomás P., O’Neill, Shane J., and McElvaney, Noel G.
- Subjects
- *
CYSTIC fibrosis , *NEUTROPHILS - Abstract
Cystic fibrosis is characterised in the lungs by high levels of neutrophil elastase (NE). NE induces interleukin-8 (IL-8) expression via an IL-1 receptor-associated kinase signalling pathway. Here, we show that these events involve the cell surface membrane bound toll-like receptor 4 (TLR4). We demonstrate that human embryonic kidney (HEK)293 cells transfected with a TLR4 cDNA (HEK-TLR4) express TLR4 mRNA and protein and induce IL-8 promoter activity in response to NE. Treatment of both HEK-TLR4 and human bronchial epithelial cells with NE decreases TLR4 protein expression. Furthermore, a TLR4 neutralising antibody abrogates NE-induced IL-8 production, and induces tolerance to a secondary lipopolysaccharide stimulus. These data implicate TLR4 in NE induced IL-8 expression in bronchial epithelium. [Copyright &y& Elsevier]
- Published
- 2003
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