Open AccessJournal Article
Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.
Katsuaki Hoshino,Osamu Takeuchi,Taro Kawai,Hideki Sanjo,Tomohiko Ogawa,Yoshifumi Takeda,Kiyoshi Takeda,Shizuo Akira +7 more
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TLDR
It is demonstrated that TLR4 is the gene product that regulates LPS response, and a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family is found.Abstract:
The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and B cells from TLR4-deficient mice did not respond to LPS. All these manifestations were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. Furthermore, C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family. Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-κB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response.read more
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Book ChapterDOI
MyD88 as a Bottle Neck in Toll/IL-1 Signaling
Osamu Takeuchi,Shizuo Akira +1 more
TL;DR: Analysis of MyD88-deficient mice revealed its essential role in TLR/IL-1R signaling as well as in both the innate and the adaptive immune response.
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Endotoxin/Lipopolysaccharide Activates NF-κB and Enhances Tumor Cell Adhesion and Invasion Through a β1 Integrin-Dependent Mechanism
Jiang Huai Wang,Brian J. Manning,Qiong Di Wu,Siobhan Blankson,David Bouchier-Hayes,H. Paul Redmond +5 more
TL;DR: Direct evidence is provided that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-κB, up-regulate β1 integrin expression, and subsequently promote tumor cell adhesion and invasion, which is β1 subunit-dependent.
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Suppression of Bladder Epithelial Cytokine Responses by Uropathogenic Escherichia coli
TL;DR: In this in vitro model system, cystitis strains of UPEC have genes encoding factors that suppress proinflammatory cytokine production by bladder epithelial cells.
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Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/IL-1 domain containing adaptor inducing IFN-β
Tomonori Hirotani,Masahiro Yamamoto,Yutaro Kumagai,Satoshi Uematsu,Ichiro Kawase,Osamu Takeuchi,Shizuo Akira +6 more
TL;DR: Taken together, MyD88 and TRIF play both redundant and distinct roles in LPS-induced gene expression, with proinflammatory cytokines and chemokines being induced quickly after LPS stimulation and regulated by mRNA stability as well as transcription.
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Knockout of toll-like receptor-4 attenuates the pro-inflammatory state of diabetes.
TL;DR: TLR4 contributes to the pro-inflammatory state and TLR4KO attenuates inflammation in diabetes, according to this study, which was examined using the streptozotocin-induced diabetic mouse model.
References
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Journal ArticleDOI
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,Christophe Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Silva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,Betsy Layton,Bruce Beutler +13 more
TL;DR: The mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane.
Journal Article
Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,C. Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Suva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,B. Layton,Bruce Beutler +13 more
Journal ArticleDOI
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
TL;DR: The cloning and characterization of a human homologue of the Drosophila toll protein (Toll) is reported, which has been shown to induce the innate immune response in adult Dosophila.
Journal ArticleDOI
The Dorsoventral Regulatory Gene Cassette spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults
TL;DR: It is shown that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection and the intracellular components of the dorsoventral signaling pathway and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults.
Journal ArticleDOI
Innate Immunity: The Virtues of a Nonclonal System of Recognition
TL;DR: Characterization of the nonclonal receptors of the innate immune system responsible for the adjuvant activity, and, evidently, for the associated side effects, would provide a powerful alternative approach, which would ultimately allow one to target these receptors directly.