CD14/toll-like receptor 4 (TLR4) intracellular signalling complex

CD14/toll-like receptor 4 (TLR4) intracellular signalling complex: lipopolysaccharide (LPS) binds to serum LPS binding protein (LBP) and is transferred to the glycosyl phosphatidylinositol (GPI) linked CD14 receptor, which interacts with the signalling receptor TLR4 and the accessory protein MD-2. Leucine-rich repeats (LRRs) in the extracellular domain of toll family proteins have been implicated in the recognition of pathogens. LPS stimulates the activation of various mitogen activated protein kinase (MAPK) pathways, such as extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. These pathways activate various transcription factors, including Elk-1, c-Jun, c-Fos, activating transcription factor 1 (ATF-1), ATF-2, serum response factor, and cAMP response element binding protein. In addition, LPS activates the nuclear factor κB (NF-κB) pathway through myeloid differentiation protein 88 (MyD88), interleukin 1 (IL-1) receptor associated kinase (IRAK), and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6). Activated inhibitory κB kinase β(IKKβ) phosphorylates inhibitory κB (IκB) and permits nuclear translocation of NF-κB/Rel complexes, such as p50/p65. LPS stimulation of monocytes/macrophages induces many inflammatory mediators, such as cytokines (TNF-α, IL-1, IL-2, IL-6, and granulocyte, macrophage, and granulocyte-macrophage colony stimulation factors), adhesion molecules (E selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1), chemokines (IL-8, macrophage chemotactic protein 1), receptors (tissue factor, IL-2Rα), and inflammatory enzymes (inducible nitric oxide synthase and cyclo-oxygenase 2, etc). AP-1, activating protein 1; CRE, cAMP response element; SRE, serum response element.

Publication

CD14 and toll-like receptor 4: a link between infection and acute coronary events?. (2004) R Arroyo-Espliguero, et al. Heart. 2004 Sep;90(9):983-988. Figure: F1. Homo sapiens

Disease mentions