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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Toll‐like receptor 4 expression levels determine the degree of LPS‐susceptibility in mice
Christoph Kalis,Benoît Kanzler,Annalisa Lembo,Alexander Poltorak,Chris Galanos,Marina A. Freudenberg +5 more
TL;DR: In macrophages, investigation of the LPS‐induced cytokine (IL‐6) response revealed a linear relationship between the response and the logarithm ofTLR4–MD‐2 levels, indicating that TLR4 is the only limiting factor for LPS responsiveness in Cr mice.
Journal ArticleDOI
Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease.
Hui-Hui Tan,M. Isabel Fiel,Qinghua Sun,Jinsheng Guo,Ronald E. Gordon,Lung Chi Chen,Scott L. Friedman,Joseph A. Odin,Jorge Allina +8 more
TL;DR: Ambient PM(2.5) exposure may be a significant risk factor for NAFLD progression and was evaluated by standardized histological assessment of hepatic inflammation and fibrosis.
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Histamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall components
Jaya Talreja,Mohammad H. Kabir,Michael B. Filla,Daniel J. Stechschulte,Kottarappat N. Dileepan +4 more
TL;DR: It is demonstrated that histamine up‐regulates the expression of TLR2 and TLR4 and amplifies endothelial cell inflammatory responses to Gram‐negative and Gram‐positive bacterial components.
Journal ArticleDOI
Nuclear factor-kappa B activation and innate immune response in microbial pathogen infection.
TL;DR: Exploration of the mechanisms that influence NF-kappa B activity could contribute to a better understanding of the molecular pathogenesis of microbial infections and could be important for potential therapeutic intervention that may be relevant in a wide variety of inflammatory diseases.
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Roles of Glycosylphosphatidylinositols of Toxoplasma gondii INDUCTION OF TUMOR NECROSIS FACTOR-α PRODUCTION IN MACROPHAGES
Françoise Debierre-Grockiego,Nahid Azzouz,Jörg C. Schmidt,Jean-François Dubremetz,Hildegard Geyer,Rudolf Geyer,Ralf Weingart,Richard R. Schmidt,Ralph T. Schwarz +8 more
TL;DR: It is shown that GPIs highly purified from T. gondii tachyzoites, as well as their core glycans, induce TNFα production in macrophages, supporting the idea that T. Gondii GPIs are bioactive factors that participate in the production of TNF α during toxoplasmal pathogenesis.
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
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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.
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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.
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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.