A5046704747- Immune Response and Inflammation
- Carbohydrate Chemistry and Synthesis
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Antimicrobial Peptides and Activities
- Pediatric health and respiratory diseases
- Pneumonia and Respiratory Infections
- Chemical Synthesis and Analysis
- Immunotherapy and Immune Responses
- Helicobacter pylori-related gastroenterology studies
- Influenza Virus Research Studies
- Lipid Membrane Structure and Behavior
- Galectins and Cancer Biology
- Photoreceptor and optogenetics research
- Eicosanoids and Hypertension Pharmacology
- T-cell and B-cell Immunology
- Retinal Development and Disorders
- Bacterial Infections and Vaccines
- Synthesis and Biological Evaluation
- Liquid Crystal Research Advancements
- Invertebrate Immune Response Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Fluorine in Organic Chemistry
- Metabolism and Genetic Disorders
- Click Chemistry and Applications
Keio University
2016-2025
Kindai University
2024
Osaka University
2012-2023
Ichinomiya Municipal City Hospital
2021
Toyon (United States)
2016
Kyushu University
2011
University of Occupational and Environmental Health Japan
2011
Japan Society for the Promotion of Science
2011
Osaka University of Pharmaceutical Sciences
1994-2010
Suntory Foundation for Life Sciences
2010
Nod1 is a member of family intracellular proteins that mediate host recognition bacterial peptidoglycan. To characterize immune responses mediated by Nod1, synthetic ligand compounds possessing enhanced ability to stimulate were developed study the function Nod1. Stimulation epithelial cells with stimulatory molecules induced chemokines and other proinflammatory are important for innate recruitment acute inflammatory cells. Administration ligands into mice cells, an activity was abolished in...
Two types of synthetic peptidoglycan fragments, diaminopimelic acid (DAP)-containing desmuramylpeptides (DMP) and muramyldipeptide (MDP), induced secretion interleukin (IL)-8 in a dose-dependent manner human monocytic THP-1 cells, although high concentrations compounds are required as compared with chemically synthesized Toll-like receptor (TLR) agonists mimicking bacterial components: TLR2 agonistic lipopeptide (Pam3CSSNA), TLR4 lipid A (LA-15-PP) TLR9 CpG DNA. We found marked synergistic...
Abstract Carbohydrate recognition is essential for growth, cell adhesion and signalling in all living organisms. A highly conserved carbohydrate binding module, LysM, found proteins from viruses, bacteria, fungi, plants mammals. LysM modules recognize polysaccharides containing N -acetylglucosamine (GlcNAc) residues including peptidoglycan, an component of the bacterial wall. However, molecular mechanism underpinning LysM–peptidoglycan interactions remains unclear. Here we describe basis...
Abstract Mesothelial cells that line the serous cavities and outer surface of internal organs are involved in inflammatory responses induced by microbial stimuli bacterial infection. Upon exposure to products, mesothelial secrete chemokines, but signaling pathways which these recognize bacteria mediate innate immune remain largely unknown. We report stimulation primary peritoneal via nucleotide-binding oligomerization domain (Nod)1, a member intracytoplasmic Nod-like receptor family, potent...
Oral epithelium might be the first barrier against oral bacteria in periodontal tissue. We hypothesized that is endowed with innate immune receptors for bacterial components, which play roles host defense infection without being accompanied by excessive inflammatory responses. found clear expression of Toll-like receptor (TLR)4 as well TLR2, and strong NOD1 NOD2 normal epithelial tissues immunohistochemical analysis. also showed primary cells culture expressed these molecules using PCR, flow...
Nod1 and Nod2 are intracellular proteins that involved in recognition of bacterial molecules their genetic variations have been linked to several inflammatory diseases strongly affected by environmental factors. However, the distribution Nod1- Nod2-stimulatory different species environments is unknown. Here we established a quantitative bioassay screen characterize activities sites species. Using this system, found common including foods soils contain high levels activities. Several Bacillus...
LPS, a principal membrane component in Gram-negative bacteria, is recognized by receptor complex consisting of TLR4 and MD-2. MD-2 an extracellular molecule that associated with the domain has critical role LPS recognition. directly interacts region from Phe(119) to Lys(132) (Arg(132) mice) been shown be important for interaction between TLR4/MD-2. With mouse mutants, we show this study Gly(59) was found novel amino acid binding outside 119-132. signaling thought triggered ligand-induced...
Peptidoglycan recognition proteins (PGRPs), a novel family of pattern molecules (PRMs) in innate immunity conserved from insects to mammals, recognize bacterial cell wall peptidoglycan (PGN) and are suggested act as anti-bacterial factors. In humans, four kinds PGRPs (PGRP-L, -Iα, -Iβ -S) have been cloned all human bind PGN. this study, we examined the possible regulation expression oral epithelial cells upon stimulation with chemically synthesized pathogen-associated molecular patterns...
The goal of this study was to investigate the effects stimulants for a nucleotide-binding domain, leucine-rich repeat-containing (NLR) protein family on human artery endothelial cells and murine arteries.Human coronary were challenged in vitro with microbial components that stimulate NLRs or Toll-like receptors. We found stimulatory NLR receptor ligands adhesion molecule expression cytokine secretion by cells. On basis these results, we examined vivo mice. Among them, FK565, 1...
Abstract Helicobacter pylori is a common cause of gastroduodenal inflammatory diseases such as chronic gastritis and peptic ulcers also an important factor in gastric carcinogenesis. Recent reports have demonstrated that bacterial processes, stimulation with H. lipopolysaccharide (LPS), initiate atherosclerosis. To establish the structures responsible for response LPS, we synthesized various kinds lipid A (i.e., triacylated Kdo‐lipid compounds), or without ethanolamine group at 1‐phosphate...
Abstract Alcaligenes faecalis is the predominant Gram‐negative bacterium inhabiting gut‐associated lymphoid tissues, Peyer's patches. We previously reported that an A. lipopolysaccharide (LPS) acted as a weak agonist for Toll‐like receptor 4 (TLR4)/myeloid differentiation factor‐2 (MD‐2) well potent inducer of IgA without excessive inflammation, thus suggesting LPS might be used safe adjuvant. In this study, we characterized structure both lipooligosaccharide (LOS) and from . synthesized...
Abstract The lipid A of LPS activates TLR4 through an interaction with myeloid differentiation protein-2 (MD-2) and the degree acylation affects responsiveness. Two single nucleotide polymorphisms (Asp299Gly Thr399Ile) have been associated hyporesponsiveness. We hypothesized that combination hypoacylation these would exhibit a compounded effect on signaling. HEK293T transfectants expressing wild-type or polymorphic were stimulated Escherichia coli (predominantly hexaacylated A) Shigella...
Natural killer (NK) cells are lymphocyte effectors that activated to control certain microbial infections and tumors. Many NK-activating regulating receptors involved in NK cell function. In addition, activation of naïve is fundamentally triggered by cytokines or myeloid dendritic (mDC) various modes. this study, we synthesized 16 S-[2,3-bis(palmitoyl)propyl]cysteine (Pam2Cys) lipopeptides with sequences designed from lipoproteins Staphylococcus aureus, assessed their functional properties...
Abstract Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls and exhibit various immunobiological activities. Two types minimum essential PGN structures for activities were chemically synthesized designated as muramyldipeptide; N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), which common both Gram-positive Gram-negative bacteria, well most some respectively. Recently, intracellular receptors MDP iE-DAP have been demonstrated...
The peptidoglycan (PG) bacterial cell wall glycoconjugate has been well known as a strong immunopotentiator. Partial structures of PG were chemically synthesized for elucidation precise biological activities. Effective construction distinct repeating glycans was accomplished by the coupling key disaccharide glucosaminyl-β(1–4)-muramic acid unit. Stereoselective glycosylation units achieved neighboring group participation N-Troc (Troc = 2,2,2-trichloroethoxycarbonyl) and appropriate...
Staphylococcus aureus is known to activate mammalian immune cells through Toll-like receptor 2 (TLR2). We recently demonstrated that a lipoprotein fraction obtained from S. by Triton X-114 phase partitioning potent activator of TLR2. In this study, we separated TLR2-activating lipoproteins expressed in and characterized an N-terminal structure. The was prepared glass bead disruption followed partitioning. molecules were mainly detected the mass range 30–35 kDa. Seven identified spectra their...
The structural prerequisites for lipopolysaccharide (LPS) and its partial structures the activation of Limulus clotting cascade (Limulus amebocyte lysate [LAL] test) are described compared with corresponding requirements human immune cells such as mononuclear cells. A necessary, but not sufficient, motif this is presence 4 ′ -phosphate-diglucosamine backbone recognition structure (‘epitope’) in lipid A. High activity only expressed by assemblies endotoxins, largely independent type...
Abstract TLR4/MD-2 senses lipid A, activating the MyD88-signaling pathway on plasma membrane and TRIF-signaling after CD14-mediated internalization into endosomes. Monophosphoryl A (MPL), a detoxified derivative of is weaker than in MyD88-dependent pathway. Little known, however, about mechanisms underlying attenuated activation pathways. We here show that MPL was impaired induction CD14-dependent dimerization compared with A. Impaired decreased TNFα production. In contrast, comparable to...