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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Why is neuroimmunopharmacology crucial for the future of addiction research
TL;DR: It is hoped that by combining the collective wisdom of neuroscience, immunology and pharmacology, into Neuroimmunopharmacology, the authors may more fully understanding the neuronal and immune complexities of how drugs of abuse, such as opioids, create their rewarding and addiction states.
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Involvement of Toll-Like Receptor 4 Signaling in Interferon-γ Production and Antitumor Effect by Streptococcal Agent OK-432
Masato Okamoto,Tetsuya Oshikawa,Tomoyuki Tano,Go Ohe,Sachiko Furuichi,Hidetomo Nishikawa,Sharif Uddin Ahmed,Sachiko Akashi,Kensuke Miyake,Osamu Takeuchi,Shizuo Akira,Yoichiro Moriya,Shuzo Matsubara,Yoshiki Ryoma,Motoo Saito,Mitsunobu Sato +15 more
TL;DR: TLR4 and MD-2 may mediate OK-432-induced anticancer immunity and be associated with the in vivo IFN-gamma induction in 19 patients administeredOK-432.
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Production and mechanism of secretion of interleukin-1β from the marine fish gilthead seabream
TL;DR: The combination of LPS and VaDNA was found to be synergistic, suggesting that each ligand is recognized by a different pattern recognition receptor, and addition of extracellular ATP does not promote IL-1beta secretion by immune cells and fails to induce phosphatidylserine flip.
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Haemophilus influenzae porin induces Toll-like receptor 2-mediated cytokine production in human monocytes and mouse macrophages.
Marilena Galdiero,Massimiliano Galdiero,Emiliana Finamore,Fabio Rossano,Maria Elsa Gambuzza,Maria Rosaria Catania,Giuseppe Teti,Angelina Midiri,Giuseppe Mancuso +8 more
TL;DR: The data indicate that the TLR2/MyD88 pathway plays an essential role in Hib porin-mediated cytokine production, and may be useful in the development of alternative therapies aimed at reducing excessive inflammatory responses during Hib infections.
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Anti-Inflammatory Activities of Marine Algae in Neurodegenerative Diseases.
Maria Cristina Barbalace,Marco Malaguti,Laura Giusti,Antonio Lucacchini,Silvana Hrelia,Cristina Angeloni +5 more
TL;DR: The key inflammatory processes involved in neurodegeneration are highlighted and the potential of specific compounds from marine algae to counteract neuroinflammation in the CNS is highlighted.
References
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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.