Unresponsiveness of MyD88-Deficient Mice to Endotoxin

Taro Kawai; Osamu Adachi; Tomohiko Ogawa; Kiyoshi Takeda; Shizuo Akira

doi:10.1016/s1074-7613(00)80086-2

Abstract

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.

Keywords

BiologyImmunologyVirology

MeSH Terms

Adaptor ProteinsSignal TransducingAnimalsAntigensDifferentiationB-LymphocytesCalcium-Calmodulin-Dependent Protein KinasesCellsCulturedCytokinesDrosophila ProteinsEnzyme ActivationHistocompatibility Antigens Class IIImmune ToleranceImmunityInnateInterleukin-1 Receptor-Associated KinasesLipid ALipopolysaccharide ReceptorsLipopolysaccharidesLymphocyte ActivationMacrophagesPeritonealMembrane GlycoproteinsMiceMiceKnockoutMyeloid Differentiation Factor 88Protein BiosynthesisProtein KinasesProteinase Inhibitory ProteinsSecretoryProteinsReceptorsCell SurfaceReceptorsImmunologicReceptorsInterleukin-1ShockSepticToll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptors

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Publication Info

Year: 1999
Type: article
Volume: 11
Issue: 1
Pages: 115-122
Citations: 2059
Access: Closed

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APA Style

                            
                                
                                    Taro Kawai, 
                                
                                    Osamu Adachi, 
                                
                                    Tomohiko Ogawa
                                
                                et al.
                            
                            (1999). 
                            Unresponsiveness of MyD88-Deficient Mice to Endotoxin. 
                            Immunity
                            , 11
                            (1)
                            , 115-122.
                            https://doi.org/10.1016/s1074-7613(00)80086-2
                        

Identifiers

DOI: 10.1016/s1074-7613(00)80086-2
PMID: 10435584

Data Quality

Data completeness: 86%