Unresponsiveness of MyD88-deficient mice to endotoxin.
MyD88 is a general adaptor protein that plays an important role in the Toll/IL-1 receptor family signalings. Recently, Toll-like receptors 2 and 4 (TLR2 and TLR4) have been suggested to be the signaling receptors for lipopolysaccharide (LPS). In this study, we demonstrate that MyD88 knockout mice lack the ability to respond to LPS as measured by shock response, B cell proliferative response, and secretion of cytokines by macrophages and embryonic fibroblasts. However, activation of neither NF-kappaB nor the mitogen-activated protein (MAP) kinase family is abolished in MyD88 knockout mice. These findings demonstrate that signaling via MyD88 is essential for LPS response, but the inability of MyD88 knockout mice to induce LPS-dependent gene expression cannot simply be attributed to lack of the activation of MAP kinases and NF-kappaB.
Kawai
T
T
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan.
Adachi
O
O
Ogawa
T
T
Takeda
K
K
Akira
S
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors; D029721:Drosophila Proteins; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000502:physiology; D007108:Immune Tolerance / Q000235:genetics*; D007113:Immunity, Innate; D053592:Interleukin-1 Receptor-Associated Kinases; D008050:Lipid A / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012772:Shock, Septic / Q000235:genetics* / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D029721:Drosophila Proteins; D000949:Histocompatibility Antigens Class II; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases