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Chapter category: Oncology

Lipid A Receptor TLR4‑Mediated Signaling Pathways

This chapter appears in the following book:

Lipid A in Cancer Therapy

Edited by: Jean-François Jeannin
ISBN: TBA
» Get more information about this book at landesbioscience.com «

Chapter authors:
Masahiro Yamamoto and Shizuo Akira


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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 TLR4 by 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 cascades is elaborately down‑regulated by a number of negative regulators. In this review, we discuss the mechanisms of the activation or de‑activation program mediated by the Lipid A receptor TLR4.

Masahiro Yamamoto
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University

Shizuo Akira
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University

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