LPS-induced Toll-like receptor 4 signalling triggers cross-talk of apoptosis signal-regulating kinase 1 (ASK1) and HIF-1alpha protein

FEBS Lett. 2008 Jan 23;582(2):319-26. doi: 10.1016/j.febslet.2007.12.024. Epub 2007 Dec 26.


Toll-like receptor 4 (TLR4) is required for recognition of lipopolysaccharide (LPS) of Gram-negative bacteria and induction of the innate immune response to them. Nevertheless, the involvement of some crucial pathways in TLR4 signalling is poorly understood. Here, we report that LPS-induced TLR4 signalling triggers cross talk of HIF-1alpha and ASK1 in THP-1 human myeloid monocytic leukaemia cells. Both pathways are activated via redox-dependent mechanism associated with tyrosine kinase/phospholipase C-1gamma-mediated activation of protein kinase C alpha/beta, which are known to activate NADPH oxidase and the production of reactive oxygen species that activate both HIF-1alpha and ASK1. ASK1 contributes to the stabilisation of HIF-1alpha, most likely via activation of p38 MAP kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • DNA Primers
  • Enzyme Activation
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Kinase Kinase 5 / metabolism*
  • Phosphorylation
  • RNA, Messenger / genetics
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / metabolism*


  • DNA Primers
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lipopolysaccharides
  • RNA, Messenger
  • Reactive Oxygen Species
  • Toll-Like Receptor 4
  • MAP Kinase Kinase Kinase 5