Discovering differential activation machinery of the Toll-like receptor 4 signaling pathways in MyD88 knockouts

FEBS Lett. 2006 Feb 20;580(5):1457-64. doi: 10.1016/j.febslet.2006.01.046. Epub 2006 Jan 26.

Abstract

To understand differential time activation of nuclear factor kappaB (NF-kappaB) and the temporal features of the downstream pro-inflammatory cytokines' [tumour-necrosis-factor-alpha (TNF-alpha) and IP-10] mRNA levels in myeloid differentiation primary-response protein 88 (MyD88) knockouts (KOs), I developed a computational model of the TLR4 pathway. The result suggests that the late phase expression of NF-kappaB activity observed in MyD88 KOs is possibly due to a number of novel intermediates acting along the MyD88-independent pathway. I also simulate that the TNF-alpha levels will increase at a longer time in MyD88 KOs, not previously mentioned.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency*
  • Animals
  • Animals, Genetically Modified
  • Computer Simulation
  • Kinetics
  • Models, Biological*
  • Myeloid Differentiation Factor 88
  • NF-kappa B / metabolism
  • Signal Transduction*
  • Toll-Like Receptor 4 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha