獣医学科

大塚 裕忠

オオツカ ヒロタダ  (Hirotada Otsuka)

基本情報

所属
日本獣医生命科学大学 獣医解剖学教室 准教授 (博士)

J-GLOBAL ID
201701017544609751
researchmap会員ID
B000285933

論文

 29
  • Hirotada Otsuka, Naoko Nonaka, Masanori Nakamura, Satoshi Soeta
    Journal of oral biosciences 2023年6月19日  査読有り筆頭著者責任著者
    OBJECTIVES: Histidine decarboxylase (HDC), a histamine synthase, is expressed in various tissues and is induced by proinflammatory cytokines such as TNFα. As they age, C57BL/6 mice show auto-antibody deposition and lymphocyte infiltration into various tissues, including salivary glands. However, the mechanism underlying cell infiltration and the change in HDC expression in salivary glands with aging remain unclear. Thus, we aimed to elucidate the relationship between histamine and inflammaging. METHODS: We investigated the change in histology and HDC expression in the major salivary glands (parotid, submandibular, and sublingual) of 6-week- and 9-month-old wild-type mice. We also determined the histological changes, cytokine expression, and anti-aging factor Klotho in the salivary glands of 9-month-old wild-type and HDC-deficient (HDC-KO) mice. RESULTS: Cell infiltration was observed in the submandibular gland of 9-month-old wild-type mice. Although most cells infiltrating the submandibular glands were CD3-positive and B220-positive lymphocytes, CD11c-positive and F4/80-positive monocyte lineages were also detected. HDC, TNFα, and IL-1β mRNA expression increased in the submandibular gland of 9-month-old wild-type mice. The expression of PPARγ, an anti-inflammatory protein, declined in 9-month-old wild-type mice, and Klotho expression increased in 9-month-old HDC-KO mice. Immunohistochemistry showed that Klotho-positive cells disappeared in the submandibular gland of 9-month-old wild-type mice, while Klotho was detected in all salivary glands in HDC-KO mice of the same age. CONCLUSION: Our findings demonstrate the multifunctionality of histamine and can aid in the development of novel therapeutic methods for inflammatory diseases such as Sjogren's syndrome and age-related dysfunctions.
  • Mami Araki, Syunya Noguchi, Yoshiaki Kubo, Akiko Yasuda, Miki Koh, Hirotada Otsuka, Makoto Yokosuka, Satoshi Soeta
    Research in Veterinary Science 2023年4月  査読有り
  • Mami Araki, Syunya Noguchi, Yoshiaki Kubo, Akiko Yasuda, Miki Koh, Hirotada Otsuka, Makoto Yokosuka, Satoshi Soeta
    Journal of Comparative Pathology 200 35-45 2023年1月  査読有り
  • Hirotada Otsuka, Yasuo Endo, Hiroshi Ohtsu, Satoshi Inoue, Syunya Noguchi, Masanori Nakamura, Satoshi Soeta
    International journal of hematology 113(3) 348-361 2021年1月4日  査読有り筆頭著者
    Histidine decarboxylase (HDC), a histamine synthase, is expressed in various hematopoietic cells and is induced by hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF). We previously showed that nitrogen-containing bisphosphonate (NBP)-treatment induces extramedullary hematopoiesis via G-CSF stimulation. However, the function of HDC in NBP-induced medullary and extramedullary hematopoiesis remains unclear. Here, we investigated changes in hematopoiesis in wild-type and HDC-deficient (HDC-KO) mice. NBP treatment did not induce anemia in wild-type or HDC-KO mice, but did produce a gradual increase in serum G-CSF levels in wild-type mice. NBP treatment also enhanced Hdc mRNA expression and erythropoiesis in the spleen and reduced erythropoiesis in bone marrow and the number of vascular adhesion molecule 1 (VCAM-1)-positive macrophages in wild-type mice, as well as increased the levels of hematopoietic progenitor cells and proliferating cells in the spleen and enhanced expression of bone morphogenetic protein 4 (Bmp4), CXC chemokine ligand 12 (Cxcl12), and hypoxia inducible factor 1 (Hif1) in the spleen. However, such changes were not observed in HDC-KO mice. These results suggest that histamine may affect hematopoietic microenvironments of the bone marrow and spleen by changing hematopoiesis-related factors in NBP-induced extramedullary hematopoiesis.
  • Hirotada Otsuka, Yasuo Endo, Hiroshi Ohtsu, Satoshi Inoue, Mutsuki Kuraoka, Miki Koh, Hideki Yagi, Masanori Nakamura, Satoshi Soeta
    Anatomical record (Hoboken, N.J. : 2007) 304(5) 1136-1150 2020年10月9日  査読有り筆頭著者
    Histidine decarboxylase (HDC), histamine synthase, is expressed in hematopoietic stem cells and in lineage-committed progenitors in the bone marrow (BM). However, the role of histamine in hematopoiesis is not well described. To evaluate the role of histamine in hematopoiesis, we analyzed the changes in HDC expression at hematopoietic sites, the BM, spleen, and liver of 2-, 3-, and 6-week old wild-type mice. We also performed morphological analyses of the hematopoietic sites using HDC-deficient (HDC-KO) mice. In wild-type adults, HDC expression in the BM was higher than that in the spleen and liver and showed an age-dependent increase. Histological analysis showed no significant change in the adult BM and spleen of HDC-KO mice compared to wild-type mice. In the liver, HDC expression was temporarily increased at 3 weeks, and decreased at 6 weeks of age. Morphological analysis of the liver revealed more numerous hematopoietic colonies and megakaryocytes in HDC-KO mice compared to wild-type mice at 2 and 3 weeks of age, whereas no changes were observed in adults. Most of these hematopoietic colonies consisted of B220-positive B-lymphocytes and TER119-positive erythroblasts and were positive for the cell proliferation marker PCNA. Notably, these hematopoietic colonies declined in HDC-KO mice upon N-acetyl histamine treatment. A significant increase in the expression of hematopoiesis-related cytokines, IL3, IL7, EPO, G-CSF, and Cxcl12 was observed in the liver of 3-week old HDC-KO mice compared to wild-type mice. These results suggest that histamine-deficiency may maintain an environment suitable for hematopoiesis by regulating hematopoiesis-related cytokine expression in the liver of postnatal mice. This article is protected by copyright. All rights reserved.

MISC

 24
  • 黄美貴, 倉岡睦季, 大塚裕忠, 添田聡, 尼崎肇
    日本獣医学会学術集会講演要旨集 166th 2023年  
  • Miki Koh, Syunya Noguchi, Mami Araki, Hirotada Otsuka, Makoto Yokosuka, Satoshi Soeta
    The Journal of veterinary medical science 82(6) 745-753 2020年6月24日  査読有り
    Vascular endothelial growth factor-A (VEGF-A) is a principal regulator of hematopoiesis as well as angiogenesis. However, the functions of VEGF-A and its receptors (VEGFRs) in the differentiation of mast cells (MCs) in the skin remain unclear. The aim of this study was to determine the expression patterns of two VEGFRs (Flk1 and Flt1) in the skin MCs during development and maturation in rats. From the 17th days of embryonic development (E17) to 1 day after birth (Day 1), most of skin MCs were immature cells containing predominant alcian blue (AB)+ rather than safranin O (SO)+ granules (AB>SO MCs). AB>SO MC proportions gradually decreased, while mature AB<SO MC proportions increased from Day 7 to 28. Flk1+ MC proportions increased from E20 and reached to approximately 90% from Day 1 to 21, thereafter decreased to about 10% at Day 60 and 90. Flk1+ MC proportions changed almost in parallel with the numbers of MCs and Ki67+ MC proportions from E17 to Day 90. The proportions of MCs with both nuclear and cytoplasmic Flt1-immunoreactivity were markedly increased at Day 28, when the proportions of nuclear Flk1+, Ki67+, and AB>SO MCs had significantly decreased, and AB<SO MC proportions significantly increased. Considering that the main function of Flt1 is suppression of Flk1 effects, our results indicated that cross-talk between Flk1 and Flt1 regulates the proliferation and maturation of the skin MCs during late embryonic and neonatal development in rats.
  • 中村 雅典, 八木 秀樹, 大塚 裕忠, 遠藤 康男
    炎症と免疫 27(6) 463-468 2019年10月  査読有り招待有り
    造血は出生後、骨髄で営まれる。したがって骨形成と造血は密接に関連し、その破綻は多くの疾患につながると考えられる。ビスフォスフォネート(BPs)は、非加水分解性のP-C-P構造をもつピロリン酸類似化合物である。BPsは骨に強く結合し、骨吸収の過程で破骨細胞に取り込まれ、骨吸収を強力にに持続的に抑制する。BPsには分子内に窒素をもつもの(N-BPs)ともたないもの(non-N-BPs)があり、N-BPsの骨吸収抑制作用はnon-N-BPsよりもはるかに強いが、発熱や消化管障害等の副作用が報告されている。筆者らはマウスへのN-BPs投与で、骨髄での赤血球造血の消失と赤血球造血の脾臓での亢進を見出した。また、コラーゲン誘導関節炎モデルへのN-BPs投与による骨破壊の亢進が誘導されることから、破骨細胞以外による骨破壊が起こることを示した。本稿では、N-BPsの造血動態と骨破壊に対する影響、ならびに造血動態の異常と骨破壊の関連性について、これまで筆者らが得たデータについて解説する。(著者抄録)
  • 中村雅典, 八木秀樹, 大塚裕忠, 遠藤康男
    炎症と免疫 27(6) 19-24 2019年  
  • 大塚裕忠, 大塚裕忠, 角山優輔, 遠藤康男, 大津浩, 大津浩, 中村雅典, 添田聡
    日本解剖学会総会・全国学術集会講演プログラム・抄録集 124th 148 2019年  

書籍等出版物

 4

講演・口頭発表等

 11

担当経験のある科目(授業)

 6

共同研究・競争的資金等の研究課題

 4