LPS induction of gene expression in human monocytes.
Lipopolysaccharide (LPS [endotoxin]) is the principal component of the outer membrane of Gram-negative bacteria. Recent studies have elucidated how LPS is recognized by monocytes and macrophages of the innate immune system. Human monocytes are exquisitely sensitive to LPS and respond by expressing many inflammatory cytokines. LPS binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14. Next, LPS is transferred to the transmembrane signaling receptor toll-like receptor 4 (TLR4) and its accessory protein MD2. LPS stimulation of human monocytes activates several intracellular signaling pathways that include the IkappaB kinase (IKK)-NF-kappaB pathway and three mitogen-activated protein kinase (MAPK) pathways: extracellular signal-regulated kinases (ERK) 1 and 2, c-Jun N-terminal kinase (JNK) and p38. These signaling pathways in turn activate a variety of transcription factors that include NF-kappaB (p50/p65) and AP-1 (c-Fos/c-Jun), which coordinate the induction of many genes encoding inflammatory mediators.
Departments of Immunology, C-204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D029721:Drosophila Proteins; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000378:metabolism*; D051218:Lymphocyte Antigen 96; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases
D000954:Antigens, Surface; D029721:Drosophila Proteins; C495377:LY96 protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases