Neutrophil elastase up‐regulates interleukin‐8 via toll‐like receptor 4

FEBS Letters

Taggart, Clifford C¹  Devaney, James M¹  O'Neill, Shane J¹  Carroll, Tomás P¹  Greene, Catherine M¹  McElvaney, Noel G¹ 

[1] Respiratory Research, Department of Medicine, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland

关键词: Toll-like receptor 4;    Cystic fibrosis;    Neutrophil elastase;    CF;    cystic fibrosis;    ELISA;    enzyme-linked immunosorbent assay;    HBE;    human bronchial epithelia(l);    HEK;    human embryonic kidney;    IRAK;    interleukin-1 receptor-associated kinase;    NE;    neutrophil elastase;    TLR;    toll-like receptor;   

DOI  :  10.1016/S0014-5793(03)00482-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown