Researchers Database

tsuda hidetoshi

    DivisionofHumanGenetics Research Associate
Contact: thidetjichi.ac.jp
Last Updated :2021/10/17

Researcher Information

J-Global ID

Research Interests

  • 遺伝子解析   細胞増殖   細胞内動態   IL-33   乾癬   ケラチノサイト   

Research Areas

  • Life sciences / Dermatology

Academic & Professional Experience

  • 2013  Jichi Medical UniversitySchool of Medicine研究員

Association Memberships

  • The Japan Society of Human Genetics   The Japanese Society for Investigative Dermatology   The Molecular Biology Society of Japan   

Published Papers

  • Hioki T, Kamiya K, Tsuda H, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Journal of dermatology 46 (11) e443 - e444 0385-2407 2019/11 [Refereed][Not invited]
  • Akimasa Adachi, Mayumi Komine, Hidetoshi Tsuda, Saeko Nakajima, Kenji Kabashima, Mamitaro Ohtsuki
    The journal of allergy and clinical immunology. In practice 7 (1) 325 - 327 2213-2198 2019/01 [Refereed][Not invited]
  • Jin M, Komine M, Tsuda H, Oshio T, Ohtsuki M
    The Journal of dermatology 45 (7) 855 - 857 0385-2407 2018/07 [Refereed][Not invited]
  • Yoshitaka Ueda, Mayumi Komine, Koji Kamiya, Hidetoshi Tsuda, Takeo Maekawa, Satoru Murata, Mamitaro Ohtsuki
    Journal of Dermatology 45 (3) 326 - 328 1346-8138 2018/03 [Refereed][Not invited]
     
    A 92-year-old man developed an erythematous eruption on the trunk and extremities with numerous pustules accompanied by fever. He had never experienced pustular eruption or been diagnosed with psoriasis previously. Skin biopsy revealed Kogoj's spongiform pustule, and he was diagnosed with generalized pustular psoriasis (GPP). Genomic DNA was extracted from his peripheral blood and the sequence of IL36RN gene was analyzed, which revealed a p.Arg10X homozygous mutation. Several cases of elderly-onset GPP have been reported, however, this is the oldest case of GPP. The existence of splice variants of IL36RN was suspected, but we could not detect any splice variants of IL36RN in this case or in a healthy control from peripheral blood samples.
  • Nobuki Maki, Mayumi Komine, Hidetoshi Tsuda, Yurika Fujita, Etsuko Fujita, Satoru Murata, Toshio Demitsu, Atsushi Utani, Mamitaro Ohtsuki
    Journal of Dermatology 45 (2) 244 - 246 1346-8138 2018/02 [Refereed][Not invited]
  • Hidetoshi Tsuda, Mayumi Komine, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 85 (2) 137 - 140 0923-1811 2017/02 [Refereed][Not invited]
  • Tomoyuki Oshio, Mayumi Komine, Hidetoshi Tsuda, Shin-ichi Tominaga, Hirohisa Saito, Susumu Nakae, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 85 (2) 106 - 114 0923-1811 2017/02 [Refereed][Not invited]
     
    Background: Skin is the outermost tissue of the human body, and works as a mechanical, chemical, and biological barrier. The epidermis is the uppermost layer of the skin, and keratinocytes constitute the majority of epidermal cells. Wounds are disruptions of skin integrity, and cause tremendous disadvantages to humans; accordingly, rapid wound healing is very important. Interleukin (IL)-33 is expressed in barrier tissue cells, such as epithelial and endothelial cells. Upon injury, IL-33 is released to stimulate immune cells, functioning as an "alarmin." ST2 is a receptor for IL-33; its soluble form (s)ST2 acts as a decoy receptor and competes for IL-33 binding. Objectives: We aimed to clarify the role of IL-33 in wound healing. Materials and methods: Wild-type (WT), IL-33 knockout (IL33 KO) mice, and sST2 transgenic (Tg) mice were wounded with a 4-mm punch, and the wound healing process was compared. Immunohistochemical analyses were performed to detect macrophages, neutrophils, and mast cells. Total RNA was extracted from the skin samples and real-time PCR was performed. An in vitro scratch wound assay was performed. Results: Wound healing was delayed in IL33 KO mice compared to WT mice, while wound healing in sST2 Tg mice was comparable to that of WT mice. A histological examination showed delayed elongation of the epidermal tongue in IL-33 KO mice. An immunohistochemical study revealed prolonged neutrophilic infiltration at a later stage in IL-33 KO mice. IL-6, IL-1 beta, and CXCL1 transcripts were more abundant in the wounds of IL-33 KO mice than WT mice. Intraperitoneal administration of an NF kappa B inhibitor to IL-33 KO mice normalized the delayed wound healing and the enhanced expression of IL-6 in IL-33 KO mice. Epidermal keratinocytes from IL-33 KO mice showed delayed wound closure compared to those from WT mice. Conclusion: Our results indicate that nuclear IL-33, but not IL-33 as a cytokine, has beneficial effects on wound healing in mice, probably by suppressing NF kappa B to inhibit excessive inflammation and by maintaining keratinocyte proliferation or migration for epithelialization. (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Akimasa Adachi, Mayumi Komine, Tomoko Hirano, Hidetoshi Tsuda, Masaru Karakawa, Satoru Murata, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (12) 1439 - 1440 0385-2407 2016/12 [Refereed][Not invited]
  • Akimasa Adachi, Mayumi Komine, Satoru Murata, Hidetoshi Tsuda, Yuta Kawahara, Akira Morimoto, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (11) 1377 - 1378 0385-2407 2016/11 [Refereed][Not invited]
  • Etsuko Fujita, Mayumi Komine, Hidetoshi Tsuda, Akimasa Adachi, Satoru Murata, Yasuyuki Kamata, Seiji Minota, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 42 (12) 1169 - 1171 0385-2407 2015/12 [Refereed][Not invited]
     
    We describe a case of H syndrome with massive skin involvement, retroperitoneal fibrosis and Raynaud's phenomenon. A 48-year-old man with parents of a consanguineous marriage, first appeared with decreased urine output, skin sclerosis on his inner thighs and short stature (142 cm, 47 kg). The patient had suffered from hearing loss since the age of 1 year, and his secondary sexual characteristics had not developed. Computed tomography showed periaortic fibrosis, bilateral ureteral stenosis, hydronephrosis and sclerosis of the germinal cords. A biopsy from the retroperitoneal mass revealed remarkable fibrosis with chronic inflammatory cells. Biopsies from the skin lesion showed thick collagen bundles through the dermis and lymphohistiocytic infiltration with numerous plasma cells. Serum inflammatory markers, such as C-reactive protein, vascular endothelial factor, transforming growth factor-beta and soluble interleukin-2 receptor, were elevated. Prednisolone was effective in treating skin lesions and in lowering serum inflammatory markers. After a long period of follow up, genomic DNA of the patient was obtained, and we identified a homozygous mutation in exon 5, c.625G>A, which caused transition of glycine to arginine, p.Gly208Arg, in the patient, but not in DNA samples from another 50 healthy individuals. This is the first case of H syndrome with Raynaud's phenomenon and retroperitoneal fibrosis, and the first Japanese case of H syndrome reported in the English published work with a novel mutation in the SLC29A3 gene.
  • Shin-ichi Tominaga, Kenji Tago, Hidetoshi Tsuda, Mayumi Komine
    CYTOKINE 72 (1) 105 - 108 1043-4666 2015/03 [Refereed][Not invited]
     
    The interleukin-33 (IL-33)-ST2L signaling pathway has been shown to play important roles in the field of immunology, especially as a trigger for allergic reactions such as bronchial asthma. However, coming back to the original finding that the ST2 gene is induced during initiation of the cell cycle of fibroblastic cell lines, the possible functions of the ST2 gene products and their specific ligand, IL-33, in the field of cell growth regulation are still interesting problems to be solved. In this study, we used NIH-3T3 mouse cell line and added IL-33 before and after cell proliferation assay, which revealed the dual function of IL-33. When IL-33 was added to the confluent cells before the start of cell proliferation, it suppressed the cell growth concentration-dependently. On the other hand, if IL-33 was added after the start of cell proliferation, it enhanced the cell growth. The negative effect of IL-33 on cell proliferation is a novel finding and would provide an important clue to the roles of IL-33 and ST2/ST2L in growth regulation. (C) 2014 Elsevier Ltd. All rights reserved.
  • Masaru Karakawa, Mayumi Komine, Yasushi Hanakawa, Hidetoshi Tsuda, Koji Sayama, Kunihiko Tamaki, Mamitaro Ohtsuki
    JOURNAL OF CELLULAR PHYSIOLOGY 229 (12) 1935 - 1945 0021-9541 2014/12 [Refereed][Not invited]
     
    The cutaneous T cell-attracting chemokine (CTACK)/CCL27 is indispensable in skin inflammation. CTACK/CCL27 is exclusively produced by epidermal keratinocytes to attract CCR10-expressing T lymphocytes to the skin. We investigated the mechanism of CTACK/CCL27 production from normal human epidermal keratinocytes (NHEKs) by the proinflammatory cytokines TNF and IFN. CTACK/CCL27 production was induced by TNF via ERK, JNK, p38, and NFB. The induction of CTACK/CCL27 by TNF was suppressed by IFN via a pathway dependent on JAK, STAT1, and STAT3. Our results also demonstrated that IFN and TNF induced the phosphorylation of EGFR and the following phosphorylation of ERK, which is partly responsible for the suppressive effect of IFN on TNF-induced production of CTACK/CCL27. Peri-lesional skin of psoriasis demonstrates early inflammatory changes as we have previously reported. CTACK/CCL27 expression was diffuse in the peri-lesional epidermis, while it was restricted to basal layer in lesional epidermis, suggesting that CTACK/CCL27 expression was induced in the early stage of psoriatic plaque formation, and IFN could participate in the suppression of CTACK/CCL27 expression in the lesional epidermis, reflecting the later stage of psoriatic plaque formation. Our study suggests that CTACK/CCL27 may have a pivotal role in the early stage of psoriasis plaque formation, but should be downregulated in the later stage to induce inflammation characteristic for chronic psoriasis plaques. J. Cell. Physiol. 229: 1935-1945, 2014. (c) 2014 Wiley Periodicals, Inc.
  • Jitlada Meephansan, Mayumi Komine, Hidetoshi Tsuda, Masaru Karakawa, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 71 (2) 107 - 114 0923-1811 2013/08 [Refereed][Not invited]
     
    Background: Interleukin (IL)-33 is a dual functional, IL-1 family member cytokine, whose exact roles in inflammatory skin diseases are still unknown. IL-17A is a key cytokine in the pathogenesis of psoriasis. Objectives: We investigated if IL-17A could induce IL-33 in epidermal keratinocytes, and the signaling mechanisms involved. Methods: IL-33 levels were evaluated by RT-PCR and western blot in human keratinocytes following IL-17A simulation. IL-33 immunohistochemical staining of psoriatic skin samples was also performed and compared with that of control tissues. The role of signaling pathways downstream of IL-17A was investigated using small molecule inhibitors of EGFR, ERK, p38, and JAK. Adenovirus vector expressing dominant negative STAT1 was also utilized. Results: IL-33 and its receptor, ST2L, were expressed in the psoriatic epidermis, and the associated infiltrating cells. IL-17A induced IL-33 expression at mRNA and protein levels in a time- and concentration-dependent manner. IL-17A caused phosphorylation of EGFR, ERK, p38, and STAT1. IL-17A-induced IL-33 expression was blocked by the addition of EGFR, ERK, p38, and JAK inhibitors, and dominant negative STAT1-expressing adenovirus vector. Conclusion: IL-17A induced IL-33 in NHEKs through EGFR, ERK, p38, and JAK/STAT1 pathways, which were necessary for the induction of IL-33. IL-33, induced by IL-17A in epidermal keratinocytes, may be involved in the pathophysiology of inflammatory skin diseases, including psoriasis. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Hiroyoshi Tsuchiya, Junji Sato, Hidetoshi Tsuda, Yoko Fujiwara, Toshiyuki Yamada, Akio Fujimura, Taka-aki Koshimizu
    Toxicology 305 79 - 88 0300-483X 2013/03 [Refereed][Not invited]
     
    The tocolytic agent ritodrine acts on the β2-adrenoceptor and is an effective treatment option for preterm labor. However, several adverse effects of ritodrine therapy, including liver damage, have been noted. To elucidate the underlying mechanisms of ritodrine-induced adverse effects, development of sensitive biomarkers of these adverse events is necessary. Here, we report the development and analysis of an animal model of ritodrine-induced liver damage. Female mice received daily ritodrine injections for 2 weeks liver samples were then collected and subjected to DNA microarray analysis. Ritodrine significantly altered the expression of genes related to steroid and lipid metabolism, as well as the metabolism of ritodrine itself. Importantly, expression of the acute-phase reactant serum amyloid A (SAA) significantly increased after ritodrine injection, with values indicating the largest fold-change. This large increase in blood SAA levels serves as a more sensitive biomarker than conventional liver enzymes, such as aspartate aminotransferase and alanine aminotransferase. The increase in SAA expression is specific to ritodrine-induced liver damage, because SAA expression was not induced by other hepatotoxic drugs such as acetaminophen, valproic acid, or metformin. Our in vitro studies showed that cyclic adenosine 3',5'-monophosphate (cAMP) accumulation was not a primary cause of the ritodrine-induced SAA increase. Instead, SAA expression was enhanced by indirect phosphorylation of the signal transducer and activator of transcription-3 (STAT3) mediated by interleukin-6. Therefore, our study provides a method for sensitive and early detection of hepatic injury, and may thus help preclude serious liver damage due to ritodrine use in preterm labor. © 2013 Elsevier Ireland Ltd.
  • Shin-ichi Tominaga, Morisada Hayakawa, Hidetoshi Tsuda, Satoshi Ohta, Ken Yanagisawa
    Biochemical and Biophysical Research Communications 430 (3) 969 - 974 0006-291X 2013/01 [Refereed][Not invited]
     
    Interleukin-33 (IL-33) is a dual-function molecule that regulates gene expression in nuclei and, as a cytokine, conveys proinflammatory signals from outside of cells via its specific receptor ST2L. There are still a lot of questions about localization and processing of IL-33 gene products. In the course of re-evaluating human IL-33 gene, we found distinct promoter usage depending on the cell type, similar to the case in the ST2 gene. Furthermore, we found a novel exon 2E in the conventional intron 2 whose open reading frame corresponded to a transmembrane protein of 131 amino acids. Dependence of exon 2E expression on differentiation of HUVEC cells is of great interest in relation to human IL-33 function. © 2012 Elsevier Inc.
  • Jitlada Meephansan, Mayumi Komine, Satomi Hosoda, Hidetoshi Tsuda, Masaru Karakawa, Satoru Murata, Toshio Demitsu, Mamitaro Ohtsuki
    JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 68 (1) 138 - 143 0190-9622 2013/01 [Refereed][Not invited]
     
    Background: Degos disease or malignant atrophic papulosis is a rare occlusive vasculopathic disease characterized by pathognomonic cutaneous lesions and frequently fatal systemic involvement. The etiology of malignant atrophic papulosis remains unclear, and there is currently no effective treatment for malignant atrophic papulosis. Several chemokines can potentiate and expand the platelet response to increase thrombus formation. Among these chemokines, this study examined the expression of stromal cell-derived factor (SDF)-1/CXCL12, which is secreted by bone-marrow stromal and endothelial cells, activates megakaryocyte precursors, and costimulates platelet activation. Objective: We sought to investigate and compare the expression of SDF-1/CXCL12 in tissue sections taken from 2 patients with Degos disease, 2 patients with other vaso-occlusive diseases, and 2 healthy control subjects. Methods: Immunohistochemical staining involving antibodies to SDF-1/CXCL12 was performed on 3 skin biopsy specimens taken from 2 patients with Degos disease, 1 from a patient with antiphospholipid syndrome, 1 from a patient with cryoglobulinemia, and 2 from healthy control subjects. Results: Strong SDF-1/CXCL12 staining was observed in the infiltrating inflammatory cells in the perivascular, intravascular, and perineural areas in tissue samples from patients with Degos disease. No staining was observed in samples from patients with antiphospholipid syndrome or cryoglobulinemia or from healthy control subjects. Limitations: The number of cases available for evaluation was small. The findings were based primarily on the immunohistochemical results and were not confirmed using other techniques. Conclusions: The intense staining of SDF-1/CXCL12 in lesions attributed to Degos disease, demonstrated for the first time to our knowledge in this study, suggests SDF-1/CXCL12 involvement in the pathogenesis of the disease. (J Am Acad Dermatol 2013;68:138-43.)
  • J. Meephansan, M. Komine, H. Tsuda, M. Ohtsuki
    CLINICAL AND EXPERIMENTAL DERMATOLOGY 37 (8) 889 - 896 0307-6938 2012/12 [Refereed][Not invited]
     
    Background. Vitamin D3 is a potent regulator of cell growth, differentiation and death, tumour invasion, and angiogenesis. Production of matrix metalloproteinase (MMP)-9 and MMP-13 by tumour cells may promote tumour growth, invasion and metastasis. Aim. To investigate whether calcipotriol could suppress the expression of MMP-9 and MMP-13 in a human squamous cell carcinoma (SCC) cell line (DJM cells), and to examine the mechanism of modulation of MMP-9 and MMP-13 by calcipotriol in DJM cells treated with tumour necrosis factor (TNF)-a. Methods. Protein and mRNA levels of MMP-9 and MMP-13 were examined by ELISA and real-time PCR, respectively. Activation of signalling cascades was assessed using several inhibitors of signalling molecules and western blot analysis. Results. Production of MMP-9 and MMP-13 markedly increased when the cells were treated with TNF-a. Calcipotriol suppressed the production of MMP-9 and MMP-13 mRNA and proteins significantly, in a dose-dependent manner. Induction of MMP-9 by TNF-a was suppressed by an extracellular signal-regulated kinase (ERK) inhibitor but not by a p38 inhibitor, whereas induction of MMP-13 was inhibited by a p38 inhibitor but not by an ERK inhibitor. Calcipotriol inhibited the phosphorylation of both ERK and p38, as shown by western blotting. Conclusion. Calcipotriol reduces MMP-9 and MMP-13 production through inhibiting the phosphorylation of ERK and p38, respectively.
  • Jitlada Meephansan, Hidetoshi Tsuda, Mayumi Komine, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 132 (11) 2593 - 2600 0022-202X 2012/11 [Refereed][Not invited]
     
    IL-33, a member of the IL-1 family, is implicated in type 2 T helper cell immune reactions and acts as an "alarmin" to induce activation of dendritic cells in response to external stimuli. We investigated the effect of inflammatory cytokines on IL-33 expression in normal human epidermal keratinocytes. IFN-gamma dose- and time-dependently induced IL-33 expression in protein and mRNA; this was dependent on extracellular signal-regulated kinase, p38, EGFR, and JAK phosphorylation. Combined IFN-gamma and tumor necrosis factor (TNF)-alpha treatment induced expression of a 20-kDa band corresponding to mature IL-33, which was abolished by the addition of a calpain inhibitor. The addition of the inhibitor to IFN-gamma and TNF-alpha-stimulated cells also induced strong expression of a 25-kDa band. Small interference (si) RNA for IL-33 abolished expression of the smaller bands and the 30-kDa IL-33 band, suggesting that these IL-33 forms were IL-33 transcription products. Recombinant IL-33 added in the medium induced IL-8 production, and RNA knockdown by siRNA enhanced IL-8 expression, suggesting its dual role as a cytokine and a nuclear factor. These results indicate that IL-33 has a role in inflammatory skin diseases, in which IFN-gamma and TNF-alpha are present in high levels.
  • Hidetoshi Tsuda, Mayumi Komine, Masaru Karakawa, Takafumi Etoh, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 132 (11) 2661 - 2664 0022-202X 2012/11 [Refereed][Not invited]
  • Satomi Hosoda, Mayumi Komine, Masaru Karakawa, Hidetoshi Tsuda, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 39 (10) 855 - 857 0385-2407 2012/10 [Refereed][Not invited]
  • Koji Wakatabi, Mayumi Komine, Jitlada Meephansan, Yasushi Matsuyama, Hidetoshi Tsuda, Shin-ichi Tominaga, Mamitaro Ohtsuki
    EUROPEAN JOURNAL OF DERMATOLOGY 22 (3) 333 - 336 1167-1122 2012/05 [Refereed][Not invited]
     
    Soluble ST2 (sST2) is a soluble form of the transmembrane receptor for interleukin (IL)-33, ST2L, and is a member of the IL-1 receptor family. sST2 antagonizes IL-33-ST2L signaling by competing with ST2L as a decoy receptor for IL-33. We investigated the sST2 and IL-33 levels in the sera and bullous fluid of bullous pemphigoid patients and compared these with the corresponding levels in normal healthy controls. As controls, we used the bullous fluid of burn patients and that from suction blisters induced in normal healthy volunteers. The serum sST2 concentrations of bullous pemphigoid patients were higher than those of healthy controls. Serum sST2 levels correlated with the area of skin involvement and serum lactate dehydrogenase levels, suggesting that serum sST2 levels reflect disease severity. The sST2 concentrations in bullous fluid from bullous pemphigoid patients were higher than those from controls. The concentration of IL-33 ligand was below the detectable limits in all enzyme-linked immunosorbent assay samples. Thus, our study suggested that the serum sST2 level may be a useful marker of disease severity and that sST2 functions as a negative regulator in the pathophysiology of bullous pemphigoid.
  • Jitlada Meephansan, Mayumi Komine, Hidetoshi Tsuda, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 65 (1) 72 - 74 0923-1811 2012/01 [Refereed][Not invited]
  • Taka-aki Koshimizu, Hiroyoshi Tsuchiya, Hidetoshi Tsuda, Yoko Fujiwara, Katsushi Shibata, Akira Hirasawa, Gozoh Tsujimoto, Akio Fujimura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 392 (4) 603 - 607 0006-291X 2010/02 [Refereed][Not invited]
     
    Cellular adaptations to chronic opioid treatment result in enhanced responsiveness of adenylate cyclase and an increase in forskolin- or agonist-stimulated cAMP production. It is, however, not known whether chaperone molecules such as heat shock proteins contribute to this adenylate cyclase sensitization. Here, we report that treatment of cells with geldanamycin, an inhibitor of heat shock protein 90 (Hsp90), led to effective attenuation of morphine-induced adenylate cyclase sensitization. In SK-N-SH human neuroblastoma cells, morphine significantly increased RNA transcript and protein levels of type I adenylate cyclase, leading to sensitization. Whole-genome tiling array analysis revealed that cAMP response element-binding protein, an important mediator for cellular adaptation to morphine, associated with the proximal promoter of Hsp90AB1 not only in SK-N-SH cells but also in rat PC12 and human embryonic kidney cells. Hsp90AB1 transcript and protein levels increased significantly during morphine treatment, and co-application of geldanamycin (0.1-10nM) effectively suppressed the increase in forskolin-activated adenylate cyclase activation by 56%. Type I adenylate cyclase, but not Hsp90AB1, underwent significant degradation during geldanamycin treatment. These results indicate that Hsp90 is a new pharmacological target for the suppression of adenylate cyclase sensitization induced by chronic morphine treatment. (C) 2010 Elsevier Inc. All rights reserved.
  • Kentarou Ushijima, Shu-ichi Tsuruoka, Hidetoshi Tsuda, Gohki Hasegawa, Yuri Obi, Tae Kaneda, Masaki Takahashi, Tomohiro Maekawa, Tomohiro Sasaki, Taka-aki Koshimizu, Akio Fujimura
    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 68 (2) 194 - 200 0306-5251 2009/08 [Refereed][Not invited]
     
    center dot Cranberry juice has a significant inhibitory effect on CYP2C9 activity in vitro, whereas it shows a minimal effect on the pharmacokinetics and pharmacodynamics of warfarin, a CYP2C9 substrate in vivo. center dot Information regarding the interaction between cranberry juice and other medications metabolized by CYP2C9 is limited. WHAT THIS STUDY ADDS center dot Cranberry juice suppressed the metabolism of diclofenac, another CYP2C9 substrate, by human liver microsomes. center dot Pharmacokinetic parameters of diclofenac were not altered by cranberry juice consumption in human subjects. AIM To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9. METHODS The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics. RESULTS Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects. CONCLUSIONS Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations.
  • S Inoue, H Tsuda, T Tanaka, M Kobayashi, Y Magoshi, J Magoshi
    NANO LETTERS 3 (10) 1329 - 1332 1530-6984 2003/10 [Refereed][Not invited]
     
    Atomic force microscopy was adopted to study the nanoscopic structure formation of natural fibrous protein, fibroin from the Samia cynthia ricini wild silkworm. We have observed highly ordered nanoscale textile-fabric-like structures of fibroin molecules. From AFM and SDS-PAGE experiments, it was revealed that fibroin molecules have a rigid rodlike structure and form aggregates by end-to-end interactions of molecules. By analogy with Bombyx mori fibroin, S. c. ricini fibroin is supposed to assemble by electrostatic interactions of molecules.
  • J Magoshi, T Tanaka, H Sasaki, M Kobayashi, Y Magoshi, H Tsuda, MA Becker, S Inoue, K Ishimaru
    BIOMACROMOLECULES 4 (3) 778 - 782 1525-7797 2003/05 [Refereed][Not invited]
     
    The relation between the uptake of atmospheric CO2 and insect's production of silk fiber has not yet been reported. Here, we provide the first quantitative demonstrations that four species of silkworms (Bombyx mori, Samia cynthia ricini, Antheraea pernyi, and Antheraea yamamai) and a silk-producing spider (Nephila clavata) incorporate atmospheric CO2 into their silk fibers. The abundance of C-13 incorporated from the environment was determined by mass spectrometry and C-13 NMR measurements. Atmospheric CO2 was incorporated into the silk fibers in the carboryl groups of alanine, aspartic acid, serine, and glycine and the C-gamma of aspartic acid. We show a simple model for the uptake of atmospheric CO2 by silkworms. These results will demonstrate that silkworm has incorporated atmospheric CO2 into silk fiber via the TCA cycle; however, the magnitude of uptake into the silk fibers is smaller than that consumed by the photosynthesis in trees and coral reefs.
  • T Tanaka, J Magoshi, Y Magoshi, S Inoue, M Kobayashi, H Tsuda, MA Becker, S Nakamura
    JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY 70 (3) 825 - 832 1418-2874 2002 [Refereed][Not invited]
     
    The thermal properties of liquid silk from domestic and wild silkworms are investigated. Liquid silks obtained from the silk gland of the domesticated silkworm, Bombyx mori and four wild silkworms, Samia cynthia ricini, Dictyoploca japonica, Antheraea pernyi and Antheraea yamamai were used. The DSC curves for the liquid silk from the domestic silkworm have weak endothermic peaks corresponding to the breaking of hydrogen bonds in the a-form or to the untangling of physical network. The DSC curves for the wild silk-worm silks, however, show clear exothermic peaks corresponding to a phase transition from the alpha-helix conformation to the beta-form. Liquid silk from all the different silkworms undergoes a characteristic irreversible phase transition.

MISC

Industrial Property Rights

Research Grants & Projects

  • 新規乾癬病因候補遺伝子PTRF/CAvon-1の細胞機能解析と乾癬病態への関与
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 津田 英利
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2016/04 -2019/03 
    Author : Tduda Hidetoshi
     
    IL-33 is expressed in nucleus of epithelial and endothelial cells, and knockdown of IL-33 increased binucleated cells and decreased cell proliferation in normal human epidermal keratinocytes (NHEKs). This cause was to attenuate function of contractile ring for cytokinesis. Time laps observation revealed that cell division failed to cytokinesis. In the other hand, IL-33 expression plasmids which expressed various length of IL-33 were transfected to NHEKs, and it was irradiated UVB. IL-33 transfected NHEKs did not gain the tolerance for UVB. And addition, IL-33 transfected cells did not obtain cell proliferation. In order to examine the function of IL-33 against to psoriasis, it was investigated imiquimod induced mouse model. Imiquimod induced inflammation was significantly reduced in IL-33KO mice.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2016/04 -2019/03 
    Author : Komine Mayumi, Jin Meijuan, Tsuda Hidetoshi
     
    Transgenic mice expressing IL-33 in the suprabasal layer of epidermal keratinocytes were generated, by utilizing involucrin promoter. Transgenic mice grew slower and small, and died in 4th week. Skin, lung, lymph node and spleen was harvested in 3rd week, and histologically, immunohistochemically studied. RNA was extracted from each sample, which was subjected to DNA microarray. IL-33Tg mice showed very strong inflammation in hands and feet, with extensive inflammatory cells in the joints. The results of microarray is now being analyzed.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2013/04 -2016/03 
    Author : Tsuda Hidetoshi
     
    IL-33 is expressed in the nucleus of epithelial and endothelial cells. In this study, it was investigated that the effect of IL-33 knockdown (KD) with siRNA in normal human epidermal keratinocytes (NHEKs). IL-33 KD attenuated BrdU uptake.The cell cycle analysis found that the number of cells in G2/M phase was increased in IL-33 KD cells.Immunofluorescence study revealed that there were many binucleated cells in IL33 KD cell culture, which were scarcely found in control cells. Western blot analysis revealed that IL-33 KD cells showed attenuated myosin light chain phosphorylation, which was reported to associate with contractile ring formation. Reduced expression of Ect2 was observed, which would have caused reduced activation of RhoA. These results suggest that nuclear IL-33 is positively involved in cell proliferation through promoting contractile ring formation by positively regulating myosin light chain phosphorylation, expression of Ect2, and activation of RhoA in NHEKs.
  • カイコ細胞におけるウイルス特異的認識タンパク質の同定
    日本学術振興会:科学研究費助成事業 特別研究員奨励費
    Date (from‐to) : 2002 -2005 
    Author : 津田 英利
     
    カイコに感染するウイルスの中で唯一非感受性品種が確立されている濃核病ウイルス(DNV)のキャプシドタンパク質に反応する宿主因子の検索を目的とした。DNVには2種類が知られており、DNV-1とDNV-2と分類されている。これらウイルスはカイコの中腸円筒細胞のみで増殖し、他の細胞や非感受性品種では全く感染増殖しないとされている。両方のキャプシドタンパク質をコードしている領域をクローニングして、GST融合タンパク質を作成した。これを元に中腸タンパク質に対するウエストウエスタンを行った結果、感受性品種と非感受性品種で違いが見られた。また感受性品種に感染させてもほとんど発病しない5齢では非感受性品種と同じ様なシグナルが得られた。またDNVの研究が進んでいない一つの原因に、感染可能な培養細胞系が確立されていない事が上げられるが、カイコ中腸で非感受性特異的に見られたシグナルが培養細胞にも見られるかどうかを数種類のカイコ培養細胞タンパク質を用いて調べた。その結果、非感受性と同様のシグナルを示す細胞系と、感受性品種に近いシグナルを示す細胞系とが見つかった。これら培養細胞にそれぞれのDNVを段階希釈して感染させ、感染後のウイルスDNAをPCRによって検出した結果、良く感染し、増殖するものとそうでないものがあることが解った。これらの事より、ウイルス構造タンパク質に親和性のある宿主タンパク質は存在するが、それは感染を促進すると言うよりもむしろ、感染を防御するような働きのあるタンパク質があるのではないかと考えられた。


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.