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Lipid A in Cancer Therapy pp 59–68Cite as

Lipid A Receptor TLR4-Mediated Signaling Pathways

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 667))

Abstract

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.

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Authors and Affiliations

  1. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan

    Masahiro Yamamoto & Shizuo Akira

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  1. Masahiro Yamamoto
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  2. Shizuo Akira
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Correspondence to Shizuo Akira .

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  1. Tumor Immunology and Immunotherapy Laboratory Ecole Practique des Hautes Etudes Inserm U866, University of Burgundy, Dijon, France

    Jean-François Jeannin

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Yamamoto, M., Akira, S. (2009). Lipid A Receptor TLR4-Mediated Signaling Pathways. In: Jeannin, JF. (eds) Lipid A in Cancer Therapy. Advances in Experimental Medicine and Biology, vol 667. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1603-7_6

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