M Takeuchi

Kyoto Sangyo University, Kioto, Kyōto, Japan

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Publications (48)121.07 Total impact

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    ABSTRACT: Skin photoageing is a complex, multifactorial process and both intrinsic and extrinsic factors may contribute to its pathogenesis. The ultraviolet-irradiated hairless mouse has been used as an animal model for photoageing, but this model mimics only the 'extrinsic' aspects. Here, we show that skin from old SAMP1 mice, a model for higher oxidative stress and senescence acceleration, exhibited histological and gene expression changes similar to those in human photoaged skin without ultraviolet irradiation. These changes include an increase in elastic fibre and glycosaminoglycan histologically, an upregulation of several proinflammatory cytokines and matrix metalloproteinases, and an increase in lipid peroxide. We propose that SAMP1 mice are a spontaneous animal model for photoageing caused by an exaggerated intrinsic mechanism, namely, higher oxidative status. This mouse model is useful to explore the link between oxidative stress and photoageing, and to evaluate the efficacy of antioxidants.
    Experimental Dermatology 01/2013; 22(1):62-4. · 4.12 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado; 05/2011
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    ABSTRACT: The emergence of drug-resistant microorganisms is an important medical and social problem. Drug-resistant microorganisms are thought to grow selectively in the presence of antibiotics. Most clinically isolated drug-resistant microorganisms have mutations in the target genes for the drugs. While any of the many mutagens in the environment may cause such genetic mutations, no reports have yet described whether these mutagens can confer drug resistance to clinically important microorganisms. We investigated how environmental mutagens might be implicated in acquired resistance to antibiotics in clinically important microorganisms, which causes human diseases. We selected mutagens found in the environment, in cigarette smoke, or in drugs, and then exposed Pseudomonas aeruginosa to them. After exposure, the incidence of rifampicin- and ciprofloxacin-resistant P. aeruginosa strains markedly increased, and we found mutations in genes for the antibiotic-target molecule. These mutations were similar to those found in drug-resistant microorganisms isolated from clinical samples. Our findings show that environmental mutagens, and an anticancer drug, are capable of inducing drug-resistant P. aeruginosa similar to strains found in clinical settings.
    FEMS Microbiology Letters 04/2011; 317(2):109-16. · 2.72 Impact Factor
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    ABSTRACT: Interleukin-28B (IL-28B), also referred to as interferon-λ3, belongs to the type III interferon family. Earlier studies showed that IL-28B suppresses proliferation of some tumor cells in vitro. IL-28B gene transfection ex vivo also resulted in growth retardation of tumor cells in mice, through either direct antiproliferative action or induction of antitumor immunity. However, it has not been reported whether in vivo therapeutic administration of recombinant IL-28B can inhibit the growth of a pre-established tumor. Here, we found that repetitive subcutaneous administration of recombinant mouse IL-28B significantly induced tumor-specific cytotoxic T lymphocytes and augmented natural killer cytolytic activity, leading to moderate suppression of the growth of a murine head and neck squamous cell carcinoma (HNSCC) cell line that was completely resistant to the direct antiproliferative effect of IL-28B. Moreover, co-administration of recombinant mouse IL-28B and cisplatin (CDDP) more significantly inhibited in vivo growth of the tumor that had been established in syngenic mice and induced tumor-specific cytotoxic T lymphocytes. The CDDP treatment induced the expression of major histocompatibility complex class I and Fas molecules on the surface of HNSCC cells both in vitro and in vivo; this may be the mechanism underlying the synergistic tumor suppression activity of IL-28B and CDDP. Unlike type I interferon, IL-28B did not suppress growth of bone marrow cells in culture. Therefore, IL-28B may be useful as a tool for a novel multidisciplinary therapy against cancer, significantly potentiating innate and adaptive antitumor immune responses, especially when co-administrated with CDDP, which is currently the first choice chemotherapeutic agent against various tumors including HNSCCs.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 03/2011; 34(2):139-48. · 3.20 Impact Factor
  • American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010
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    ABSTRACT: Exposure to cigarette smoke impairs the pulmonary immune system, including alveolar macrophage function, although the mechanisms by which this occurs are not fully elucidated. This study investigates the effect of cigarette smoke exposure on the antigen-presenting activity of alveolar macrophages, which is required for antigen-specific response to T cells. C57BL/6 mice were exposed to cigarette smoke for 10 days using a Hamburg II smoking machine, and alveolar macrophages were obtained by bronchoalveolar lavage. The antigen-presenting activity of alveolar macrophages was significantly inhibited in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. Major histocompatibility complex class II cell surface molecule-positive cells, B7-1 molecule-positive cells, and interleukin-1beta messenger RNA gene expression in alveolar macrophages were significantly decreased in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. In contrast, DNA damage and generation of superoxide and hydrogen peroxide in alveolar macrophages were significantly increased by cigarette smoke exposure. These results suggest that inhibition of the antigen-presenting activity of alveolar macrophages may result from decreased expression of major histocompatibility complex class II and B7-1 molecules and interleukin-1beta messenger RNA gene expression following cigarette smoke exposure. Furthermore, inhibition of antigen presentation in alveolar macrophage may result from DNA damage induced by excessive amounts of reactive oxygen species being generated by alveolar macrophages following cigarette smoke exposure. These findings suggest that cigarette smoke impairs the immunological function of alveolar macrophages and, as a result, increases the risk for pulmonary infection.
    Inhalation Toxicology 12/2009; 21(14):1229-35. · 1.89 Impact Factor
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    ABSTRACT: Dehydroepiandrosterone (DHEA), a reversible inhibitor of glucose-6-phosphate dehydrogenase (G6PD), is increasingly taken as an antioxidative and anti-ageing supplement. This study investigated the effects of DHEA on the expression of G6PD and on the state of oxidative stress in a human promyelocytic leukaemia cell line, HL60, during the differentiation to neutrophil-like cell. This study differentiated HL60 with dimethyl sulfoxide (DMSO) in the presence (DMSO-HL60/DHEA) or absence (DMSO-HL60) of DHEA. During the differentiation, activity, mRNA and protein levels of G6PD were increased. DHEA increased these levels further. DHEA by itself suppressed the production of superoxide from DMSO-HL60 upon stimulation with phorbol myristate acetate (PMA). However, DMSO-HL60/DHEA stimulated with PMA in the absence of DHEA produced superoxide and 8-oxo-deoxyguanosine more than PMA-stimulated DMSO-HL60. After addition of H(2)O(2), the ratio of reduced glutathione to oxidized glutathione was lower in DMSO-HL60/DHEA than in DMSO-HL60. These findings indicate that DHEA acts both as an antioxidant and as a pro-oxidant.
    Free Radical Research 09/2009; 43(10):922-31. · 3.28 Impact Factor
  • A Ross, KE Pinkerton, M Takeuchi
    American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California; 04/2009
  • American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California; 04/2009
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    ABSTRACT: Jungle honey (JH) is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal). After seven injections, peritoneal cells (PC) were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2) cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS) producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW) of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.
    Evidence-based Complementary and Alternative Medicine 02/2009; 2011:908743. · 1.72 Impact Factor
  • T Ishida, K E Pinkerton, M Takeuchi
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    ABSTRACT: Smokers have higher incidences of pulmonary diseases. This increased susceptibility may result from cigarette smoke (CS)-induced impairment of the pulmonary immune system. However, the mechanism(s) is not fully understood. The aim of this study was to investigate the mechanism of the effect of alveolar macrophages (AM) from CS-exposed mice on B lymphocyte proliferation stimulated with bacterial lipopolysaccharide (LPS). Mice were exposed to CS using a Hamburg smoking machine, and AM were obtained by bronchoalveolar lavage. Lymphocytes were harvested from spleen in normal mice. AM-mediated B lymphocyte proliferation stimulated with LPS was assessed by the (3)H-thymidine method, using lymphocytes as responding cells and AM from CS-exposed or non-CS-exposed mice. Generations of superoxide and hydrogen peroxide were analyzed by flow cytometry, using hydroethidine and dichlorofluorescein diacetate. AM from CS-exposed mice significantly inhibited B lymphocyte proliferation stimulated with LPS compared with AM from non-CS-exposed mice. Generations of superoxide and hydrogen peroxide were significantly increased in CS-exposed AM compared with non-CS-exposed AM. Inhibition of B lymphocyte proliferation stimulated with LPS by AM from CS-exposed mice was clearly recovered by superoxide dismutase and catalase. These results suggest that the inhibition by CS-exposed AM of LPS-induced B lymphocyte proliferation may be caused by the increased superoxide and hydrogen peroxide generation of CS. Therefore, these immunological inhibitions by CS could be associated with increased risk of pulmonary diseases.
    Respiration 12/2008; 77(1):91-5. · 2.92 Impact Factor
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    ABSTRACT: Common laboratory rats and mice fail to develop persistent, progressive pulmonary inflammation found in chronic obstructive pulmonary disease as a result of tobacco smoke exposure. We hypothesized that spontaneously hypertensive rats would be more susceptible than normal Wistar Kyoto rats to acute tobacco smoke-induced pulmonary inflammation due to impaired apoptosis. Spontaneously hypertensive rats display systemic oxidative stress, inflammation, hypercoagulation, and immunosupression, similar to humans with chronic obstructive pulmonary disease. Male spontaneously hypertensive rats and Wistar Kyoto rats were exposed whole-body to tobacco smoke (total particulate concentration 75-85 mg/m(3)) or filtered air for 6 h/day for 2 or 15 days (3 days/wk). Tobacco smoke caused an increase in bronchoalveolar lavage fluid neutrophils at both time points in each strain. Significantly more neutrophils were noted in spontaneously hypertensive rats at 15 days compared to Wistar Kyoto rats. There was a trend of increase for macrophages in spontaneously hypertensive rats at both time points (significant at 2 days). TUNEL assay detected apoptotic cells in bronchoalveolar lavage fluid and lung tissue sections. The number of apoptotic neutrophils in airway walls and bronchoalveolar lavage fluid increased at 2 days in both strains, but at 15 days the effect was much lower in spontaneously hypertensive rats than in Wistar Kyoto rats. Tobacco smoke induces a greater inflammatory response associated with lower apoptotic neutrophils in the lungs of spontaneously hypertensive rats compared to Wistar Kyoto rats. The spontaneously hypertensive rat may be a more relevant animal model of acute tobacco smoke-induced airway inflammation than other laboratory rats.
    Inhalation Toxicology 06/2008; 20(7):623-33. · 1.89 Impact Factor
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    ABSTRACT: SUMMARYIL-1 possesses pleiotropic properties on various cells and its activity may be stringently regulated in several ways. We have previously reported that both IL-1 and its inhibitory factor are concomitantly released from alveolar macrophages in both healthy subjects and patients with chronic inflammatory lung diseases. An increase in IL-1 activities and a decrease in inhibitory activities arc characteristics found in both healthy smokers and patients with interstitial lung diseases. In this study, we further examined the biological properties of IL-1 inhibitory factor. The inhibitor exhibited a dose-dependent specific inhibition of an augmentation by IL-1 of PH-nduced murinc thymocyte proliferation, while no inhibition of the augmentation by IL-2, IL-4, IL-6, or tumour necrosis factor (TNF) was found. 125I-labelled IL-1α binding on PHA-stimulated murinc thymocytes revealed two types of IL-1 binding sites. 44 sites/cell with a Kd of 2.7 ± 10−10 m and 230 sites/cell with a Kd of 2.5 ± 10−9 m. Alveolar macrophage culture supernatants blocked the binding of labelled IL-1 to the IL-1 receptor in a dos-ependent fashion. Scatchard plot analysis revealed that the inhibitory factor in the supernatants blocked the binding competitively. These results indicate that alveolar macrophages produce a specific IL-1 inhibitory factor, functioning as an IL-1 receptor antagonist.
    Clinical & Experimental Immunology 04/2008; 88(1):181-187. · 3.28 Impact Factor
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    ABSTRACT: Bronchoalveolar lavage (BAL) is useful for diagnosing various interstitial lung diseases (ILDs) and monitoring ILD during treatment. The ability to detect specific agents or substances by using BAL is especially helpful in determining whether idiopathic ILD has a background causality. BAL in combination with other intensive examinations may enable the definitive diagnosis of an idiopathic ILD. Among the idiopathic ILDs of concern, this article focuses on idiopathic interstitial pneumonia (IIP) and cryptogenic organizing pneumonia (COP). IIP and COP are classified together as idiopathic interstitial pneumonia (IIP), an integrated clinicoradiographic pathological disease entity. BAL has identified two points important for differentiating the disease entity: a paucity of lymphocytes appears in the BAL fluid of patients with idiopathic pulmonary fibrosis (IPF), and lymphocytosis with a decreased CD4:CD8 ratio appears in patients with COP. These findings can be useful, in combination with high-resolution computed tomographic (HRCT) data, for selecting a favorable treatment option. On the other hand, these rules cannot be applied to IP associated with collagen vascular disease (CVD). Furthermore, some IIP patients may manifest features of CVD during the clinical course after the detection of IP (interstitial pneumonia). Thus the definite role of BAL cell profiles remains to be determined.
    Seminars in Respiratory and Critical Care Medicine 11/2007; 28(5):496-503. · 3.02 Impact Factor
  • World Allergy Organization Journal 01/2007;
  • World Allergy Organization Journal 01/2007;
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    ABSTRACT: Dichlorofluorescin (DCFH), a widely used fluorescent probe for reactive oxygen species (ROS) was decomposed completely and generated two distinct fluorescent products by photo-irradiation at 254 nm for 30 min. In the previous study, we had shown that one was dichlorofluorescein (DCF), a well known oxidized product of DCFH. In this study we investigated the other product and identified it as monochlorofluorescein (MCF) by 1H-NMR and fast atom bombardment/mass spectrum (FAB/MS) analyses. MCF was generated by photo-irradiation, but not by ROS. On the other hand, DCF was produced by both photo-irradiation and ROS. MCF showed similar fluorescent emission spectrum to DCF, however, its fluorescence intensity was more than that of DCF. The kinetic study suggested that MCF was not generated from DCF but from monochlorofluorescin, which might be generated from DCFH by photo-irradiation.
    Free Radical Research 10/2006; 40(9):959-65. · 2.99 Impact Factor
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    ABSTRACT: The study aims at establishing a novel vaccine procedure, using bone marrow-derived DCs that have ingested apoptotic B16 melanoma (DCs(+)), alone or in combination with splenic T lymphocytes from a syngenic donor. Co-immunization with DCs(+) and T cells showed the highest antitumor potential against preestablished B16 tumor in mice, in which CTL and NK cytotoxicities were drastically elevated, while either DCs(+) alone, naive DCs (DCs(-)) alone, or a mixture of DCs(-) and T cells induced less significant therapeutic outcomes. Use of extracellular matrix proteins elevated antitumor activity of DC(-)/T cell vaccine. Compared with the CD8(+) cells, the CD4(+)T cells more remarkably improved the efficacy of DC-based immunotherapy. The present system may be a feasible therapeutic modality to eradicate malignancies including melanoma.
    Cancer Letters 09/2006; 240(1):83-93. · 5.02 Impact Factor

Publication Stats

385 Citations
121.07 Total Impact Points

Institutions

  • 1999–2013
    • Kyoto Sangyo University
      Kioto, Kyōto, Japan
  • 2002–2009
    • Kagoshima University
      • • Graduate School of Medical and Dental Sciences
      • • Faculty of Medicine
      Kagoshima-shi, Kagoshima-ken, Japan
    • Kyoto Prefectural University of Medicine
      • Department of Microbiology
      Kioto, Kyōto, Japan
  • 1988–2008
    • Kyoto University
      • • Primate Research Institute
      • • Department of Respiratory Medicine
      Kioto, Kyōto, Japan
  • 1993
    • University of the Ryukyus
      • Faculty of Medicine
      Okinawa, Okinawa-ken, Japan