The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Luciano Ribeiro Filgueiras - One of the best experts on this subject based on the ideXlab platform.
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Leukotriene B4 mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes
Science Signaling, 2015Co-Authors: Luciano Ribeiro Filgueiras, Stephanie L Brandt, Soujuan Wang, Zhuo Wang, David L Morris, Carmella Evansmolina, Raghavendra G Mirmira, Sonia Jancar, Henrique C SerezaniAbstract:Patients with type 1 diabetes have chronic systemic inflammation and are more prone to developing sepsis. Filgueiras et al. found that mice that are a model for type 1 diabetes had higher amounts of Leukotriene B4, a proinflammatory lipid, and of 5-lipoxygenase, the enzyme that produces Leukotriene B4. Mice with type 1 diabetes that were treated with an inhibitor of 5-lipoxygenase survived sepsis and had decreased markers of inflammation, suggesting that targeting 5-lipoxygenase to prevent the production of Leukotriene B4 could decrease the susceptibility of type 1 diabetic patients to sepsis.
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Leukotriene B4–mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes
Science Signaling, 2015Co-Authors: Luciano Ribeiro Filgueiras, Stephanie L Brandt, Soujuan Wang, Zhuo Wang, David L Morris, Raghavendra G Mirmira, Sonia Jancar, Carmella Evans-molina, C. Henrique SerezaniAbstract:Patients with type 1 diabetes have chronic systemic inflammation and are more prone to developing sepsis. Filgueiras et al. found that mice that are a model for type 1 diabetes had higher amounts of Leukotriene B4, a proinflammatory lipid, and of 5-lipoxygenase, the enzyme that produces Leukotriene B4. Mice with type 1 diabetes that were treated with an inhibitor of 5-lipoxygenase survived sepsis and had decreased markers of inflammation, suggesting that targeting 5-lipoxygenase to prevent the production of Leukotriene B4 could decrease the susceptibility of type 1 diabetic patients to sepsis.
Takehiko Yokomizo - One of the best experts on this subject based on the ideXlab platform.
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BLT2, a Second Leukotriene B4 Receptor
Advances in Prostaglandin and Leukotriene Research, 2020Co-Authors: Takehiko Yokomizo, Takashi Izumi, Kazuhiko Kato, Kan Terawaki, Takao ShimizuAbstract:Leukotriene B4 (LTB4) is a potent chemoattractant and activator for granulocytes and macrophages [1–3]. The high-affinity receptor for LTB4 (BLT1) was cloned and shown to be a G-protein-coupled receptor (GPCR) with low structural homology to the other known GPCRs [4]. Here we report a second LTB4 receptor, BLT2, found in a gene cluster with BLT1 [5,6]. BLT2 is the most homologous GPCR to BLT1, and is identified as a low-affinity receptor for LTB4.
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modulation of Leukotriene B4 receptor 1 signaling by receptor for advanced glycation end products rage
The FASEB Journal, 2016Co-Authors: Takako Ichiki, Toshiaki Okuno, Tomoaki Koga, Kazuko Saeki, Yasuhiko Yamamoto, Hiroshi Yamamoto, Masakiyo Sakaguchi, Takehiko YokomizoAbstract:Leukotriene B4 (LTB4) receptor 1 (BLT1), a high-affinity GPCR for LTB4, plays important roles in acute and chronic inflammatory diseases. Although the LTB4-BLT1 axis is known to promote inflammatio...
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Leukotriene B4 augments and restores fcγrs dependent phagocytosis in macrophages
Journal of Biological Chemistry, 2010Co-Authors: Fuyuki Okamoto, Kazuko Saeki, Hideki Sumimoto, Sho Yamasaki, Takehiko YokomizoAbstract:Phagocytosis by macrophages is essential for host defense, i.e. preventing invasion of pathogens and foreign materials. Macrophages engulf immunoglobulin G (IgG)-opsonized particles through the action of the receptors for the Fc of IgG (FcγRs). Leukotriene B4 (LTB4) is a classical lipid chemoattractant derived from arachidonic acid. Leukotriene B4 receptor 1 (BLT1), a high affinity LTB4 receptor, is expressed in a variety of immune cells such as neutrophils, macrophages, and dendritic cells. Although LTB4 has been shown to enhance macrophage phagocytosis, few studies have investigated the intracellular mechanisms involved in this in detail. Furthermore, there have been no reports of the direct cross-talk between LTB4-BLT1 and IgG-FcγRs signaling. Here, we show that FcγRs-dependent phagocytosis was attenuated in BLT1-deficient macrophages as compared with wild-type (WT) cells. Moreover, cross-talk between LTB4-BLT1 and IgG-FcγRs signaling was identified at the level of phosphatidylinositol 3-OH kinase (PI3K) and Rac, downstream of Syk. In addition, the trimeric Gi protein (Gi) was found to be essential for BLT1-dependent phagocytosis. Surprisingly, we found that LTB4-BLT1 signaling restores phagocytosis in the absence of FcγRs signaling. These data indicate that LTB4-BLT1 signaling plays a pivotal role in macrophage phagocytosis and innate immunity.
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Leukotriene B4 receptors.
Prostaglandins & Other Lipid Mediators, 2002Co-Authors: Akiko Toda, Takehiko Yokomizo, Takao ShimizuAbstract:Leukotriene B4 (LTB4) is a classical pro-inflammatory lipid mediator that activates and recruits neutrophils into inflammatory areas. LTB4 is an arachidonic acid-derived metabolite produced by 5-lipoxygenase and LTA4 hydrolase. To date, two Leukotriene B4 receptors, the high-affinity receptor BLT1 and the low-affinity receptor BLT2, have been cloned, and a systemic knockout mouse for each receptor has been generated. BLT1 is mainly expressed in leukocytes, but BLT2 is expressed in epithelial cells. Based on many knockout mouse studies, BLT1 is now known to play important roles in acute and chronic inflammation and immune diseases. On the other hand, BLT2 protects against colitis, accelerates epidermal wound healing, and promotes cancer progression. Thus, BLT1 and BLT2 have totally different features with respect to their expression patterns and their physiological and pathological roles. In this review, we summarize the fundamental characteristics of BLT1 and BLT2, as well as recent advances in our understanding of the biosynthesis and degradation of LTB4 and the LTB4 receptors.
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Leukotriene B4 metabolism and signal transduction
Archives of Biochemistry and Biophysics, 2001Co-Authors: Takehiko Yokomizo, Takashi Izumi, Takao ShimizuAbstract:Abstract Leukotriene B4 (LTB4) is known as one of the most potent chemoattractants and activators of leukocytes and is involved in inflammatory diseases. Enzymes involved in the biosynthesis and metabolism of LTB4 have been cloned, and their properties are well understood. Two G-protein-coupled receptors (BLT1 and BLT2) have been cloned and characterized. BLT1 and BLT2 are high- and low-affinity LTB4 receptors, respectively, and form a gene cluster in human and mouse. In this article recent findings on the metabolism of and the receptors for LTB4 are reviewed. We also discuss briefly a coreceptor role of BLT in HIV infection, and ion channel modification by LTB4.
Takao Shimizu - One of the best experts on this subject based on the ideXlab platform.
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BLT2, a Second Leukotriene B4 Receptor
Advances in Prostaglandin and Leukotriene Research, 2020Co-Authors: Takehiko Yokomizo, Takashi Izumi, Kazuhiko Kato, Kan Terawaki, Takao ShimizuAbstract:Leukotriene B4 (LTB4) is a potent chemoattractant and activator for granulocytes and macrophages [1–3]. The high-affinity receptor for LTB4 (BLT1) was cloned and shown to be a G-protein-coupled receptor (GPCR) with low structural homology to the other known GPCRs [4]. Here we report a second LTB4 receptor, BLT2, found in a gene cluster with BLT1 [5,6]. BLT2 is the most homologous GPCR to BLT1, and is identified as a low-affinity receptor for LTB4.
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na mimicking ligands stabilize the inactive state of Leukotriene B4 receptor blt1
Nature Chemical Biology, 2018Co-Authors: Tetsuya Hori, Toshiaki Okuno, Kunio Hirata, Keitaro Yamashita, Yoshiaki Kawano, Masaki Yamamoto, Masakatsu Hato, Motonao Nakamura, Takao ShimizuAbstract:A structure of Leukotriene B4 receptor BLT1 bound with a benzamidine-containing compound, BIIL260, reveals an inverse-agonist mechanism involving ligand binding in the sodium ion-centered water cluster adjacent to the conserved orthosteric site of class A GPCRs.
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Leukotriene B4 receptors.
Prostaglandins & Other Lipid Mediators, 2002Co-Authors: Akiko Toda, Takehiko Yokomizo, Takao ShimizuAbstract:Leukotriene B4 (LTB4) is a classical pro-inflammatory lipid mediator that activates and recruits neutrophils into inflammatory areas. LTB4 is an arachidonic acid-derived metabolite produced by 5-lipoxygenase and LTA4 hydrolase. To date, two Leukotriene B4 receptors, the high-affinity receptor BLT1 and the low-affinity receptor BLT2, have been cloned, and a systemic knockout mouse for each receptor has been generated. BLT1 is mainly expressed in leukocytes, but BLT2 is expressed in epithelial cells. Based on many knockout mouse studies, BLT1 is now known to play important roles in acute and chronic inflammation and immune diseases. On the other hand, BLT2 protects against colitis, accelerates epidermal wound healing, and promotes cancer progression. Thus, BLT1 and BLT2 have totally different features with respect to their expression patterns and their physiological and pathological roles. In this review, we summarize the fundamental characteristics of BLT1 and BLT2, as well as recent advances in our understanding of the biosynthesis and degradation of LTB4 and the LTB4 receptors.
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Leukotriene B4 metabolism and signal transduction
Archives of Biochemistry and Biophysics, 2001Co-Authors: Takehiko Yokomizo, Takashi Izumi, Takao ShimizuAbstract:Abstract Leukotriene B4 (LTB4) is known as one of the most potent chemoattractants and activators of leukocytes and is involved in inflammatory diseases. Enzymes involved in the biosynthesis and metabolism of LTB4 have been cloned, and their properties are well understood. Two G-protein-coupled receptors (BLT1 and BLT2) have been cloned and characterized. BLT1 and BLT2 are high- and low-affinity LTB4 receptors, respectively, and form a gene cluster in human and mouse. In this article recent findings on the metabolism of and the receptors for LTB4 are reviewed. We also discuss briefly a coreceptor role of BLT in HIV infection, and ion channel modification by LTB4.
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Characterization of the cloned guinea pig Leukotriene B4 receptor: comparison to its human orthologue.
European Journal of Pharmacology, 1999Co-Authors: Yves Boie, Takehiko Yokomizo, Takao Shimizu, Rino Stocco, Nicole Sawyer, Gillian Greig, Stacia Kargman, Deborah Slipetz, Gary P. O'neill, Kathleen M. MettersAbstract:A cDNA clone coding for the guinea pig Leukotriene B4 (BLT) receptor has been isolated from a lung cDNA library. The guinea pig BLT receptor has an open reading frame corresponding to 348 amino acids and shares 73% and 70% identity with human and mouse BLT receptors, respectively. Scatchard analysis of membranes prepared from guinea pig and human BLT receptor-transfected human embryonic kidney (HEK) 293 EBNA (Epstein–Bar Virus Nuclear Antigen) cells showed that both receptors displayed high affinity for Leukotriene B4 (Kd value of ∼0.4 nM) and were expressed at high levels (Bmax values ranging from 9 to 12 pmol/mg protein). The rank order of potency for Leukotrienes and related analogs in competition for []Leukotriene B4 specific binding at the recombinant guinea pig BLT receptor is Leukotriene B4>20-OH-Leukotriene B4>12(R)-HETE ((5Z,8Z,10E,12(R)14Z)-12-hydroxyeicosatetraen-1-oic acid)>12(S)-HETE ((5Z,8Z,10E,12(S)14Z)-12-Hydroxyeicosatetraen-1-oic acid)>20-COOH-Leukotriene B4>U75302 (6-(6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl)-1,5-hexanediol)≫Leukotriene C4=Leukotriene D4=Leukotriene E4. For the human receptor the rank order of 12(S)-HETE, 20-COOH-Leukotriene B4 and U75302 was reversed. Xenopus melanophore and HEK aequorin-based reporter gene assays were used to demonstrate that the guinea pig and human BLT receptors can couple to both the cAMP inhibitory and intracellular Ca2+ mobilization signaling pathways. However, in the case of the aequorin-expressing HEK cells (designated AEQ17-293) transfected with either the guinea pig or human BLT receptor, expression of Gα16 was required to achieve a robust Ca2+ driven response. Leukotriene B4 was a potent agonist in functional assays of both the guinea pig and human BLT receptors. U-75302 a Leukotriene B4 analogue which possesses both agonistic and antagonistic properties behaved as a full agonist of the guinea pig and human BLT receptors in AEQ17-293 cells and not as an antagonist. The recombinant guinea pig BLT receptor will permit the comparison of the intrinsic potencies of Leukotriene B4 receptor antagonists used in guinea pig in vivo models of allergic and inflammatory disorders.
Henrique C Serezani - One of the best experts on this subject based on the ideXlab platform.
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Leukotriene B4 mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes
Science Signaling, 2015Co-Authors: Luciano Ribeiro Filgueiras, Stephanie L Brandt, Soujuan Wang, Zhuo Wang, David L Morris, Carmella Evansmolina, Raghavendra G Mirmira, Sonia Jancar, Henrique C SerezaniAbstract:Patients with type 1 diabetes have chronic systemic inflammation and are more prone to developing sepsis. Filgueiras et al. found that mice that are a model for type 1 diabetes had higher amounts of Leukotriene B4, a proinflammatory lipid, and of 5-lipoxygenase, the enzyme that produces Leukotriene B4. Mice with type 1 diabetes that were treated with an inhibitor of 5-lipoxygenase survived sepsis and had decreased markers of inflammation, suggesting that targeting 5-lipoxygenase to prevent the production of Leukotriene B4 could decrease the susceptibility of type 1 diabetic patients to sepsis.
Toshiaki Okuno - One of the best experts on this subject based on the ideXlab platform.
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na mimicking ligands stabilize the inactive state of Leukotriene B4 receptor blt1
Nature Chemical Biology, 2018Co-Authors: Tetsuya Hori, Toshiaki Okuno, Kunio Hirata, Keitaro Yamashita, Yoshiaki Kawano, Masaki Yamamoto, Masakatsu Hato, Motonao Nakamura, Takao ShimizuAbstract:A structure of Leukotriene B4 receptor BLT1 bound with a benzamidine-containing compound, BIIL260, reveals an inverse-agonist mechanism involving ligand binding in the sodium ion-centered water cluster adjacent to the conserved orthosteric site of class A GPCRs.
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modulation of Leukotriene B4 receptor 1 signaling by receptor for advanced glycation end products rage
The FASEB Journal, 2016Co-Authors: Takako Ichiki, Toshiaki Okuno, Tomoaki Koga, Kazuko Saeki, Yasuhiko Yamamoto, Hiroshi Yamamoto, Masakiyo Sakaguchi, Takehiko YokomizoAbstract:Leukotriene B4 (LTB4) receptor 1 (BLT1), a high-affinity GPCR for LTB4, plays important roles in acute and chronic inflammatory diseases. Although the LTB4-BLT1 axis is known to promote inflammatio...