医学部

Tomoaki Yoshida

  (吉田 友昭)

Profile Information

Affiliation
School of Medicine Faculty of Medicine, Fujita Health University
Degree
博士(医学)

J-GLOBAL ID
200901000710044757
researchmap Member ID
1000023459

Papers

 126
  • Erdenezaya Odkhuu, Takayuki Komatsu, Naoki Koide, Yoshikazu Naiki, Kenji Takeuchi, Yukie Tanaka, Bilegtsaikhan Tsolmongyn, Ulziisaikhan Jambalganiin, Naoko Morita, Tomoaki Yoshida, Bin Gotoh, Takashi Yokochi
    Innate immunity, 24(7) 430-438, Oct, 2018  Peer-reviewed
    To suppress virus multiplication, infected macrophages produce NO. However, it remains unclear how infecting viruses then overcome NO challenge. In the present study, we report the effects of accessory protein C from Sendai virus (SeV), a prototypical paramyxovirus, on NO output. We found that in RAW264.7 murine macrophages, a mutant SeV without C protein (4C(-)) significantly enhanced inducible NO synthase (iNOS) expression and subsequent NO production compared to wild type SeV (wtSeV). SeV 4C(-) infection caused marked production of IFN-β, which is involved in induction of iNOS expression via the JAK-STAT pathway. Addition of anti-IFN-β Ab, however, resulted in only marginal suppression of NO production. In contrast, NF-κB, a primarily important factor for transcription of the iNOS gene, was also activated by 4C(-) infection but not wtSeV infection. Induction of NO production and iNOS expression by 4C(-) was significantly suppressed in cells constitutively expressing influenza virus NS1 protein that can sequester double-stranded (ds)RNA, which triggers activation of signaling pathways leading to activation of NF-κB and IRF3. Therefore, C protein appears to suppress NF-κB activation to inhibit iNOS expression and subsequent NO production, possibly by limiting dsRNA generation in the context of viral infection.
  • Yoshikazu Naiki, Takayuki Komatsu, Naoki Koide, Jargalsaikhan Dagvadorj, Tomoaki Yoshida, Moshe Arditi, Takashi Yokochi
    Innate immunity, 21(7) 770-7, Oct, 2015  
    The effect of TGF-β1 on CpG DNA-induced type I IFN production was examined by reconstituting a series of signaling molecules in TLR 3 signaling. TGF-β1 inhibited CpG DNA-induced IFN-α4 productivity in HeLa cells. Transfection of IFN regulatory factor (IRF)7 but not TNF receptor-associated factor (TRAF)6 and TRAF3 into cells triggered IFN-α4 productivity, and TGF-β1 inhibited IRF7-mediated type I IFN production in the presence of TRAF6. TGF-β1 induced ubiquitination of TRAF6, although CpG DNA did not induce it. Moreover, TGF-β1 accelerated the ubiquitination of TRAF6 in the presence of CpG DNA. TGF-β1 ubiquitinated TRAF6 at K63 but not K48. TGF-β1 also induced ubiquitination of IRF7. Further, TGF-β1 did not impair the interaction of IRF7 and TRAF6. CpG DNA induced the phosphorylation of IRF7 in the presence of TRAF6, whereas TGF-β1 inhibited the IRF7 phosphorylation. Blocking of TRAF6 ubiquitination abolished the inhibition of CpG DNA-induced type I IFN production by TGF-β. Taken together, TGF-β was suggested to inhibit CpG DNA-induced type I IFN production transcriptionally via ubiquitination of TRAF6.
  • Erdenezaya Odkhuu, Naoki Koide, Bilegtsaikhan Tsolmongyn, Ulziisaikhan Jambalganiin, Yoshikazu Naiki, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi
    Innate immunity, 21(2) 194-202, Feb, 2015  Peer-reviewed
    Here we report that LPS induces osteoclast (OC) formation in murine RAW 264.7 macrophage cells in RPMI-1640 medium but not in α-minimum essential medium (α-MEM) as the original culture medium. LPS-induced OC formation in both media was examined to clarify the differential response. Receptor activator of NF-κB ligand induced OC formation in either α-MEM or RPMI-1640 medium. However, LPS-induced OC formation in RAW 264.7 cells maintained in RPMI-1640 medium, but not α-MEM, which was also supported by mouse bone marrow-derived macrophages, although they were less sensitive to LPS than RAW 264.7 cells. LPS augmented the expression of nuclear factor of activated T-cells (NFATc1) as a key transcription factor of osteoclastogenesis in cells maintained in RPMI-1640 medium, but reduced it in cells maintained in α-MEM. A high concentration of LPS was cytotoxic against cells maintained in α-MEM. Glutathione exclusively present in RPMI-1640 medium prevented LPS-induced cell death in α-MEM and augmented LPS-induced NFATc1 expression, followed by enhanced LPS-induced OC formation. LPS induced higher generation of reactive oxygen species in α-MEM than RPMI-1640 medium. An antioxidant enhanced LPS-induced OC formation, whereas a pro-oxidant reduced it. Taken together, redox balance in the culture condition was suggested to regulate in vitro LPS-induced OC formation.
  • Naoki Koide, Erdenezaya Odkhuu, Yoshikazu Naiki, Bilegtsaikhan Tsolmongyn, Kiyoaki Ito, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi
    Innate immunity, 20(8) 816-25, Nov, 2014  Peer-reviewed
    The effect of LPS on the production of vascular endothelial growth factor (VEGF) was examined using RAW 264.7 macrophage cells. LPS induced VEGF production in RAW 264.7 cells and mouse peritoneal cells. LPS induced VEGF production via the expression of hypoxia inducible factor-1α and LPS-induced VEGF production was dependent on the activation of p38 MAPK and NF-κB activation· Transforming growth factor (TGF)-β1 augmented LPS-induced VEGF production, although TGF-β1 alone did not induce VEGF production. The augmentation of LPS-induced VEGF production by TGF-β1 was inhibited by a p38 MAPK inhibitor and was correlated with the phosphorylation of Smad3. The enhancing effect of TGF-β1 on LPS-induced VEGF production was observed in vivo in the skin lesions of mice receiving a subcutaneous injection of LPS. Taken together, it is suggested that LPS induced the VEGF production in macrophages and that it was augmented by TGF-β1 in vitro and in vivo.
  • Ulziisaikhan Jambalganiin, Bilegtsaikhan Tsolmongyn, Naoki Koide, Erdenezaya Odkhuu, Yoshikazu Naiki, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi
    International immunopharmacology, 20(1) 181-7, May, 2014  Peer-reviewed
    The inhibitory effect of valproic acid (VPA) on lipopolysaccharide (LPS)-induced inflammatory response was studied by using mouse RAW 264.7 macrophage-like cells. VPA pretreatment attenuated LPS-induced phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, but not nuclear factor (NF)-κB and mitogen-activated protein kinases. VPA reduced phosphorylation of MDM2, an ubiquitin ligase and then prevented LPS-induced p53 degradation, followed by enhanced p53 expression. Moreover, p53 small interfering RNA (siRNA) abolished the inhibitory action of VPA on LPS-induced NF-κB p65 transcriptional activation and further LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. VPA prevented LPS-induced degradation of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and up-regulated the PTEN expression. Taken together, VPA was suggested to down-regulate LPS-induced NF-κB-dependent transcriptional activity via impaired PI3K/Akt/MDM2 activation and enhanced p53 expression. A detailed mechanism for inhibition of LPS-induced inflammatory response by VPA is discussed.

Misc.

 12
  • Gantsetseg Tumurkhuu, Naoki Koide, Jargalsaikhan Dagvadorj, Abu Shadat Mohammod Noman, Imtiaz Iftakhar-E-Khuda, Yoshikazu Naiki, Takayuki Komatsu, Tomoaki Yoshida, Masataka Oda, Masahiro Nagahama, Jun Sakurai, Takashi Yokochi
    INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 305(3) 433-433, May, 2015  
  • Bilegtsaikhan Tsolmongyn, Naoki Koide, Erdenezaya Odkhuu, Abedul Haque, Yoshikazu Naiki, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi
    Cellular immunology, 282(2) 100-5, Apr, 2013  Peer-reviewed
    The effect of lipopolysaccharide (LPS) on valproic acid (VPA)-induced cell death was examined by using mouse RAW 264.7 macrophage cells. LPS inhibited the activation of caspase 3 and poly (ADP-ribose) polymerase and prevented VPA-induced apoptosis. LPS inhibited VPA-induced p53 activation and pifithrin-α as a p53 inhibitor as well as LPS prevented VPA-induced apoptosis. LPS abolished the increase of Bax/Bcl-2 ratio, which is a critical indicator of p53-mediated mitochondrial damage, in response to VPA. The nuclear factor (NF)-κB inhibitors, Bay 11-7082 and parthenolide, abolished the preventive action of LPS on VPA-induced apoptosis. A series of toll-like receptor ligands, Pam3CSK4, poly I:C, and CpG DNA as well as LPS prevented VPA-induced apoptosis. Taken together, LPS was suggested to prevent VPA-induced apoptosis via activation of anti-apoptotic NF-κB and inhibition of pro-apoptotic p53 activation. The detailed inhibitory mechanism of VPA-induced apoptosis by LPS is discussed.
  • Naoki Koide, Yoshikazu Naiki, Erdenezaya Odkhuu, Bilegtsaikhan Tsolmongyn, Takayuki Komatsu, Kiyoaki Ito, Tomoaki Yoshida, Takashi Yokochi
    Oncology research, 21(1) 59-65, 2013  Peer-reviewed
    A toll-like receptor 4 (TLR-4) ligand, lipopolysaccharide (LPS) not only activates expression and secretion of inflammatory cytokines, but it also often shows toxicity in monocytes. Whether an oncogenic protein, β-catenin, is positively involved in LPS-induced cytotoxicity in a mouse leukemic monocyte cell line, RAW 264.7, was examined. TWS119, a GSK-3β inhibitor, increased LPS-induced β-catenin accumulation in the nucleus and augmented LPS-induced cytotoxicity. Cardamonin, a β-catenin inhibitor, inhibited LPS-induced β-catenin accumulation in the nucleus and reduced LPS-induced cytotoxicity. To confirm that β-catenin is involved in LPS-induced cytotoxicity, silencing of β-catenin expression by siRNA was carried out. The results were that knockdown of β-catenin reduced LPS-induced cytotoxicity. Interestingly, Cardamonin treatment or β-catenin silencing reduced LPS-induced endoplasmic reticulum (ER) stress responses such as PERK and e1F-2α phosphorylation and CHOP expression. Moreover, TWS119 increased LPS-induced ER stress responses. On the basis of these results, the oncogenic protein β-catenin is considered to be positively involved in LPS-induced cytotoxicity, possibly by downregulating ER stress responses.
  • Naoki Koide, Akiko Morikawa, Erdenezaya Odkhuu, Abedul Haque, Battuvshin Badamtseren, Yoshikazu Naiki, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi
    Innate immunity, 18(1) 35-43, Feb, 2012  Peer-reviewed
    The LPS-mediated lethality of NC/Nga mice, having fewer NKT cells, was examined by using d-galactosamine (d-GalN)-sensitization. The NC/Nga mice were not killed by a simultaneous administration of d-GalN and LPS whereas all C57BL/6 (B6) control mice were killed. The injection of d-GalN and LPS failed to elevate the levels of serum alanine aminotransferase and caspase 3 in the liver tissues of NC/Nga mice. Further, the nitric oxide (NO) level of the d-GalN- and LPS-injected NC/Nga mice was much lower than those of the B6 mice. The expression of an inducible NO synthase (iNOS) was significantly reduced in the livers of NC/Nga mice. However, there was no significant difference in LPS-induced TNF-α production between B6 mice and NC/Nga mice. The NC/Nga mice had an impaired expression of IFN-γ protein and mRNA in response to d-GalN and LPS. The pretreatment with α-galactosylceramide (α-GalCer), which activates Vα14(+) NKT cells and induces the production of IFN-γ, rendered NC/Nga mice more susceptible to the LPS-mediated lethality. The livers of NC/Nga mice had fewer NKT cells compared to B6 mice. Taken together, it is suggested that the resistance of NC/Nga mice to the LPS-mediated lethality with d-GalN sensitization depended on the impaired IFN-γ production caused by fewer NKT cells and reduced NO production that followed.
  • Battuvshin Badamtseren, Erdenezaya Odkhuu, Naoki Koide, Abedul Hague, Yoshikazu Naiki, Shoji Hashimoto, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi
    CELLULAR IMMUNOLOGY, 270(1) 19-24, 2011  
    Thalidomide is known as an anti-angiogenic, anti-tumor, and anti-proliferative agent, widely used in the treatment of some immunological disorders and cancers. The effect of thalidomide on interferon (IFN)-gamma induced nitric oxide (NO) production in mouse vascular endothelial cells was examined in order to elucidate the anti-angiogenic or anti-inflammatory action. Thalidomide inhibited IFN-gamma-induced NO production in mouse END-D cells via reduced expression of an inducible type of NO synthase (iNOS) protein and mRNA. Since thalidomide did not alter the cell surface expression of IFN-gamma receptor, the NO inhibition was suggested to be due to the impairment of IFN-gamma-induced intracellular event by thalidomide. Thalidomide inhibited the phosphorylation of IRF1, which was required for the iNOS expression. Moreover, it inhibited the phosphorylation of STAT1, an upstream molecule of IRF1, in IFN-gamma signaling. Thalidomide did not inhibit the JAK activation in response to IFN-gamma. A phosphatase inhibitor, sodium orthovanadate, abolished the inhibitory action of thalidomide. Therefore, thalidomide was suggested to inhibit IFN-gamma-induced NO production via impaired STAT1 phosphorylation. (C) 2011 Elsevier Inc. All rights reserved.

Books and Other Publications

 4

Presentations

 1

Teaching Experience

 3

Professional Memberships

 4

Works

 1

Research Projects

 4

Social Activities

 2

教育内容・方法の工夫(授業評価等を含む)

 2
  • 件名(英語)
    医学系漢熟語の課題とテスト
    開始年月日(英語)
    2012/08
    概要(英語)
    用語の理解不足による講義からの落伍を避けることができた
  • 件名(英語)
    個別に問答を繰り返す教育
    開始年月日(英語)
    2013/10
    概要(英語)
    成績不良者とe-mailでのやり取りを通して、知識の考察、関連付けを促すことができた。

作成した教科書、教材、参考書

 1
  • 件名(英語)
    Rh不適合妊娠についての解説音声ファイル
    概要(英語)
    看護学科の学生さんに配信し、繰り返し聴いてもらって理解を深めた

その他教育活動上特記すべき事項

 2
  • 件名(英語)
    医学教育ワークショップ参加
    終了年月日(英語)
    2010/02
  • 件名(英語)
    PBLシナリオブラッシュアップ委員
    終了年月日(英語)
    2012