Lipid A Receptor TLR4-Mediated Signaling Pathways

  • Masahiro Yamamoto
  • Shizuo AkiraEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 667)


Lipid A is a strong activator of monocytes to release immune stimulators such as proinflammatory cytokines. Overproduction of inflammatory cytokines such as TNF and IL-6 is known to cause septic shock that frequently leads to multiple organ failure and finally to death. In recent years, Lipid A has also been recognized by a Toll-like receptor, TLR4. Activation of TLR4by LPS or Lipid A triggers signal transduction via the cytoplasmic domain called the Toll/IL-1 Receptor (TIR) domain. Intracellular TIR domain-containing adaptor molecules are involved in the TLR4-mediated signaling pathways. Moreover, a subset of LPS-inducible genes is regulated in two steps by the inducible nuclear protein. Additionally, the TLR4-mediated activation of signaling cascadesis elaborately down-regulated by a number of negative regulators. In this chapter, we discuss the mechanisms of the activation or de-activation program mediated by the Lipid A receptor TLR4.


Proinflammatory Cytokine Production Inducible Nuclear Protein Mutant ofTRIF 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Department of Host Defense, Research Institute for Microbial DiseasesOsaka UniversityOsakaJapan

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