Lipid A receptor TLR4-mediated signaling pathways.
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.
Yamamoto
Masahiro
M
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Akira
Shizuo
S
D006801:Humans; D008050:Lipid A / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D008050:Lipid A; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4