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

FEBS Lett. 2003 Jun 5;544(1-3):129-32. doi: 10.1016/s0014-5793(03)00482-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cystic Fibrosis / metabolism
  • DNA, Complementary / metabolism
  • Genes, Reporter
  • Humans
  • Interleukin-8 / metabolism*
  • Lasers
  • Leukocyte Elastase / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Protein Binding
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism*
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Transfection
  • Up-Regulation*


  • DNA, Complementary
  • Interleukin-8
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • RNA
  • Leukocyte Elastase