Premium
Neutrophil elastase up‐regulates interleukin‐8 via toll‐like receptor 4
Author(s) -
Devaney James M,
Greene Catherine M,
Taggart Clifford C,
Carroll Tomás P,
O'Neill Shane J,
McElvaney Noel G
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00482-4
Subject(s) - tlr4 , hek 293 cells , toll like receptor , receptor , transfection , interleukin 1 receptor , neutrophil elastase , microbiology and biotechnology , biology , signal transduction , chemistry , interleukin , inflammation , cytokine , cell culture , innate immune system , immunology , biochemistry , genetics
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.