A5101603232- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Drug Transport and Resistance Mechanisms
- Regulation of Appetite and Obesity
- Pharmacogenetics and Drug Metabolism
- Neuropeptides and Animal Physiology
- Redox biology and oxidative stress
- Receptor Mechanisms and Signaling
- Hematopoietic Stem Cell Transplantation
- Macrophage Migration Inhibitory Factor
- RNA Interference and Gene Delivery
- Pharmacological Receptor Mechanisms and Effects
- Asthma and respiratory diseases
- Sleep and Wakefulness Research
- Galectins and Cancer Biology
- Biochemical Analysis and Sensing Techniques
- Sleep and related disorders
- Heat shock proteins research
- T-cell and Retrovirus Studies
- Drug-Induced Hepatotoxicity and Protection
- Monoclonal and Polyclonal Antibodies Research
- Allergic Rhinitis and Sensitization
- Pharmacological Effects and Toxicity Studies
- Nuclear Receptors and Signaling
Juntendo University
2020-2022
RIKEN Center for Sustainable Resource Science
2018
RIKEN Center for Integrative Medical Sciences
2006-2017
Kumamoto University
2014
Tohoku University
2014
The University of Tokyo
2012
RIKEN
2012
Iwate Medical University
2012
Yamaguchi University
2012
RCA (United States)
2010
A novel and convenient method was established for the prediction of in vivo metabolic clearance human liver. The present applied vitro-in extrapolation paradigm previously rats to vitro data obtained from cryopreserved hepatocytes. Predicted hepatic availability were compared with reported oral bioavailability plasma humans 14 clinically used drugs (naloxone, buspirone, verapamil, lidocaine, imipramine, metoprolol, timolol, antipyrine, diazepam, quinidine, caffeine, propranolol, diclofenac,...
Thioredoxin-binding protein-2 (TBP-2)/vitamin D(3) up-regulated protein 1 is an endogenous molecule interacting with thioredoxin (TRX), negatively regulating TRX function, and being implicated in the suppression of tumor development metastasis. We found that TBP-2 ectopically expressed breast cancer cell line MCF-7 was localized predominantly nucleus exhibiting growth suppressive activity. The nuclear accumulation also demonstrated when cells were treated anti-cancer drug, suberoylanilide...
Abstract Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult (ATL). However, low incidence ATL among HTLV-I-infected carriers, together with a long latent period, suggests that multiple host-viral events are involved in progression HTLV-I-dependent transformation and subsequent development ATL. thioredoxin (TRX) redox active protein highly expressed HTLV-I-transformed cell lines, whereas TRX-binding protein-2/vitamin D3 up-regulated 1 (TBP-2/VDUP1) was recently...
Epidemiological studies have suggested that the recent increase in incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, underlying mechanisms remain uncertain. Here, we demonstrate natural killer T (NKT) cells mice humans play a crucial role BCG-induced suppression IgE responses. BCG-activated murine Vα14 NKT cells, but not conventional CD4 selectively express high...
Abstract Thioredoxin (TRX) is released from various types of mammalian cells despite no typical secretory signal sequence. We show here that a redox-active site in TRX essential for its release T lymphocytes response to H2O2 and extracellular regulates own H2O2-induced release. Human cell leukemia virus type I-transformed constitutively large amount TRX. The level augmented upon the addition H2O2, but suppressed N-acetylcysteine. In culture supernatant Jurkat transfectant expressing tagged...
Cardiac myosin-induced myocarditis is an experimental autoimmune (EAM) model used to investigate autoimmunological mechanisms in inflammatory heart diseases and resembles fulminant humans. We investigated the therapeutic role of thioredoxin-1 (TRX-1), a redox-regulatory protein with antioxidant antiinflammatory effects, murine EAM.EAM was generated 5-week-old male BALB/c mice by immunization porcine cardiac myosin at days 0 7. Recombinant human TRX-1 (rhTRX-1), C32S/C35S mutant rhTRX-1, or...
Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant responses. Several studies have suggested that the risk graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We developed an approach vivo expansion Tregs with RGI-2001, novel liposomal formulation synthetic derivative alpha-galactosylceramide, naturally occurring ligand binds to CD1 activates expands invariant natural...
The aim of this study was to investigate whether in vivo drug distribution brain monkeys can be reconstructed by integrating four factors: protein expression levels P-glycoprotein (P-gp)/multidrug resistance 1 at the blood-brain barrier (BBB), vitro transport activity per P-gp molecule, and unbound fractions plasma brain. For five substrates (indinavir, quinidine, loperamide, paclitaxel, verapamil) one nonsubstrate (diazepam), activities were determined measuring transcellular across...
Neuropeptide Y (NPY) is a potent feeding stimulant. The orexigenic effect of NPY might be caused in part by the action Y1 receptors. However, existence multiple receptors including possible novel receptor has made it difficult to determine relative importance regulation. Herein we certified that major using and selective antagonist (−)-2-[1-(3-chloro-5-isopropyloxycarbonylaminophenyl)ethylamino]-6-[2-(5-ethyl-4-methyl-1,3-thiazol-2-yl)ethyl]-4-morpholinopyridine (J-115814) receptor-deficient...
Neuropeptide Y (NPY) is thought to have a major role in the physiological control of energy homeostasis. Among five NPY receptors described, Y5 receptor (Y5R) prime candidate mediate some effects on homeostasis, although its physiologically relevant rodent obesity models remains poorly defined. We examined effect potent and highly selective Y5R antagonist dietary models. The selectively ameliorated diet-induced (DIO) rodents by suppressing body weight gain adiposity while improving...
Significance Both natural killer (NK) cells and γδT cells, classified as innate immune recently have been shown to features of memory cells. However, after activation, a fate invariant NK T (iNKT cells) has not identified. Here we show the presence effector memory-like KLRG1 + (Killer cell lectin-like receptor subfamily G, member 1–positive) iNKT in lung. The are able recognize respond an antigen context CD1d can persist for long time then mount potent secondary response upon encountering...
A novel and convenient in vitro method for predicting vivo metabolic clearance the liver (CL(H)) was developed. The CL(H) of a drug is usually predicted by using both unbound fraction serum intrinsic hepatic fraction, but this procedure labor-intensive. We simplified directly measuring isolated rat hepatocytes suspended called "the incubation method". Sixteen commercially available compounds reported to be mainly excreted metabolism were evaluated our method. remaining ratio unchanged after...
Adoptive transfer of regulatory T cells (Tregs) prevents graft-versus-host disease (GVHD) in mouse models, indicating a pivotal role for Tregs controlling GVHD. The present study demonstrates the efficacy pharmacologically induced vivo GVHD prevention. A single i.v. administration liposomal formulation α-galactosylceramide (RGI-2001) at time allogeneic bone marrow transplantation with spleen significantly prolonged survival mice experiencing lethal acute RGI-2001 expanded donor-derived...
Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with have yet be developed. In murine models, α-galactosylceramide (α-GalCer)-loaded, tumor antigen-expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the immune systems. current study, we established human artificial adjuvant vector (aAVC) consisting of HEK293 embryonic kidney stably transfected natural killer T...
Glycosylation inhibiting factor (GIF) and macrophage migration inhibitory (MIF) share an identical structure gene. Here we unravel two steps of posttranslational modifications in GIF/MIF molecules human suppressor T (Ts) cell hybridomas. Peptide mapping MS analysis the affinity-purified GIF from Ts cells revealed that one modification is cysteinylation at Cys-60, other phosphorylation Ser-91. Cysteinylated GIF, but not wild-type GIF/MIF, possessed immunosuppressive effects on vitro IgE...