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Ito Hiroyasu

  (伊藤 弘康)

Profile Information

Affiliation
Fujita Health University
Degree
医学博士(岐阜大学)
Researcher number
80373075
J-GLOBAL ID
201601000738827795
researchmap Member ID
7000014447
近年、Toll用受容体のリガンドやNKT細胞の活性化分子などが同定され、宿主免疫系の修飾により様々な疾患に応用されつつある。また、免疫チェックポイント分子の同定も盛んに行われており、特に癌への治療応用が期待さえている。現在、このような免疫修飾技術を持ちいて、1）完全ウイルス排除を目指したHBV感染症治療法の開発、2）癌免疫療法の開発、3）臓器再生（肝再生・皮膚創傷治癒など）方法の確立に向けて基礎的実験を行っている。

Research Interests

 29

Research Areas

 4

Research History

 11
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Education

 1

Awards

 3

Papers

 237
  • Kanata Kojima, Kouhei Sakurai, Tatsuya Ando, Yasuhiro Sakai, Mako Ochiai, Taku Kato, Hiroyasu Ito
    Medical Molecular Morphology, in press, 2025  Peer-reviewed
    Prospero homeobox protein 1 (PROX1) is aberrantly expressed in tumors, including neuroendocrine neoplasms (NENs); however, the detailed expression pattern remains elusive. This study aimed to immunohistochemically assess PROX1 expression. Immunohistochemistry (IHC) for PROX1 was performed on tissue microarrays of normal tissues (n = 107), NENs (n = 152) (small cell lung carcinoma [SCLC], lung carcinoid [LC], gastroenteropancreatic-NEN [GEP-NEN], esophageal neuroendocrine carcinoma [ENEC], medullary thyroid carcinoma [MTC], neuroblastoma [NB], and pheochromocytoma [PHEO]), and non-NENs (n = 469). In normal tissues, PROX1 was expressed in lymphatic endothelial cells and a subset of epithelial cells in the gastrointestinal tract and the distal convoluted tubules. In NENs, the positive expression was observed in the nucleus of tumor cells in 19/26 SCLC (73.1%), 13/16 LC (81.3%), 10/15 GEP-NEN (66.7%), 2/2 ENEC (100%), 17/43 MTC (39.5%), 1/25 NB (4.0%), and 0/25 PHEO (0%). Although PROX1 was negative in many non-NENs, our analysis revealed high expression in certain cases with medulloblastoma and one case with juvenile granulosa cell tumor. PROX1 was expressed in specific cases with epithelial NENs and some cases with non-NENs. Analysis of PROX1 should provide insights into the molecular characteristics of distinct tumors.
  • Taku Kato, Eiji Sugihara, Yuko Hata, Kyojiro Kawakami, Yasunori Fujita, Kosuke Mizutani, Tatsuya Ando, Yasuhiro Sakai, Kouhei Sakurai, Shohei Toyota, Hidetoshi Ehara, Masafumi Ito, Hiroyasu Ito
    The Prostate, Sep 15, 2024  
    BACKGROUND: Androgen receptor signaling inhibitors(ARSIs) have been used to treat patients with metastatic prostate cancer (PC) and castration-resistant prostate cancer (CRPC). In this study, we aimed to identify novel serum extracellular vesicle (EV)-based biomarkers to diagnose ARSI-resistance and therapeutic targets for ARSI-resistant CRPC. METHODS: Total RNA contained in serum EVs from 5 cases of CRPC before ARSI treatment and after acquiring ARSI-resistance was subjected to RNA-sequencing. The expression changes of selected RNAs contained in EVs were confirmed in 48 cases of benign prostatic hyperplasia (BPH) and 107 PC using reverse transcription-quantitative PCR (RT-qPCR) and compared with tissue RNA expression using public datasets. RESULTS: RNA-sequencing revealed that mitochondrial oxidative phosphorylation (OXPHOS)-related genes were increased in EVs after acquiring ARSI-resistance. Among them, RT-qPCR and datasets analysis demonstrated that SDHB mRNA was upregulated after acquiring ARSI-resistance in EVs and ARSI-exposed PC tissue compared to ARSI-naïve EVs and tissue, respectively. SDHB mRNA levels both in EVs and tissue were increased in localized PC compared with BPH and decreased in advanced PC. Tissue expression of SDHB mRNA was significantly correlated with those of other OXPHOS-related genes. SDHB mRNA in EVs (EV-SDHB) was elevated among 3 out of 7 ARSI-treating patients with stable PSA levels who later progressed to ARSI-resistant CRPC. CONCLUSIONS: The levels of OXPHOS-related mRNAs in EVs correlated with those in PC tissue, among which SDHB mRNA was found to be a novel biomarker to diagnose ARSI-resistance. EV-SDHB may be useful for early diagnosis of ARSI-resistance.
  • Kouhei Sakurai, Tatsuya Ando, Yasuhiro Sakai, Yuichiro Mori, Satoru Nakamura, Taku Kato, Hiroyasu Ito
    Human cell, 37(5) 1559-1566, Sep, 2024  
    Lung neuroendocrine neoplasms (NENs) are a diverse group of tumors characterized by neuroendocrine (NE) differentiation. Among lung NENs, lung carcinoid (LC) is a rare tumor with unique characteristics. Recent research has highlighted the importance of transcription factors (TFs) in establishing gene expression programs in lung NENs such as small cell lung carcinoma. However, the TFs that control the gene expression of LC are largely unknown. In this study, we report the expression and potential function of a TF called Prospero homeobox protein1 (PROX1) in LC. Publicly available transcriptome data suggested that PROX1 was highly expressed in LC tissues, which was confirmed by immunohistochemical analysis on a tissue microarray. Knockdown of PROX1 did not impact the cellular viability of an LC-derived cell line, NCI-H727. Meanwhile, transcriptome analysis revealed that PROX1 knockdown altered the expression of genes involved in NE differentiation. ASCL1, CHGA, CALCA, and LINC00261 were suggested as downstream genes of PROX1. These findings indicate that PROX1 may play an important role in the NE identity of LC by regulating the expression of key target genes.
  • Yuya Ishihara, Hiroyuki Naruse, Hidetsugu Fujigaki, Reiko Murakami, Tatsuya Ando, Kouhei Sakurai, Komei Uehara, Koki Shimomae, Eirin Sakaguchi, Hidekazu Hattori, Masayoshi Sarai, Junnichi Ishii, Ryosuke Fujii, Hiroyasu Ito, Kuniaki Saito, Hideo Izawa
    Vaccines, 12(7) 786-786, Jul 17, 2024  
    Preexisting cardiovascular disease (CVD) is a pivotal risk factor for severe coronavirus disease 2019 (COVID-19). We investigated the longitudinal (over 1 year and 9 months) humoral and cellular responses to primary series and booster doses of mRNA COVID-19 vaccines in patients with CVD. Twenty-six patients with CVD who received monovalent mRNA COVID-19 vaccines were enrolled in this study. Peripheral blood samples were serially drawn nine times from each patient. IgG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) was measured using an enzyme-linked immunosorbent assay. The numbers of interferon-γ-releasing cells in response to SARS-CoV-2 peptides were measured using an enzyme-linked immunospot assay. The RBD-IgG titers increased 2 weeks after the primary series and booster vaccination and waned 6 months after vaccination. The S1-specific T cell responses in patients aged < 75 years were favorable before and after booster doses; however, the Omicron BA.1-specific T cell responses were poor. These results suggest that regular vaccination is useful to maintain long-term antibody levels and has implications for booster dose strategies in patients with CVD. Additional booster doses, including Omicron variant-adapted mRNA vaccines, may be recommended for patients with CVD, regardless of age.
  • Kouhei Sakurai, Seiji Yamada, Rika Ito, Mako Ochiai, Tatsuya Ando, Yasuhiro Sakai, Taku Kato, Hiroyasu Ito
    Non-coding RNA Research, 9(1) 76-83, Mar, 2024  Peer-reviewed
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Misc.

 98
  • Hirofumi Ohtaki, Hiroyasu Ito, Kazuki Ando, Tetsuya Ishikawa, Masato Hoshi, Tatsuya Ando, Manabu Takamatsu, Akira Hara, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima
    Biochimica et Biophysica Acta - Molecular Basis of Disease, 1842 1464-1471, Jan 1, 2014  
    Indoleamine 2,3-dioxygenase (IDO), an enzyme that is ubiquitously distributed in mammalian tissues and cells, converts tryptophan to kynurenine, and is also known as a key molecule that promotes apoptosis in lymphocytes and neurons. In this study, we established hepatitis B virus (HBV)-transgenic (Tg)/IDO-knockout (KO) mice and examined the influence of IDO in a murine fulminant hepatitis model induced by HBV-specific cytotoxic T lymphocytes (CTL). An increase of IDO expression in the livers of HBV-Tg/IDO-wild-type (WT) mice administered HBV-specific CTL was confirmed by real-time polymerase chain reaction, western blotting, and evaluating IDO activity. Plasma alanine aminotransferase (ALT) levels in HBV-Tg/IDO-KO mice after HBV-specific CTL injection significantly decreased compared with those in HBV-Tg/IDO-WT mice. An inhibitor of IDO, 1-methyl- d-tryptophan (1-MT), could also attenuated the observed liver injury induced by this HBV-specific CTL. The expression levels of cytokine and chemokine mRNAs in the livers of HBV-Tg/IDO-WT mice were higher than those in the livers of HBV-Tg/IDO-KO mice. The administration of kynurenine aggravated the liver injury in HBV-Tg/IDO-KO mice inje
  • 石川哲也, 石上雅敏, 伊藤弘康
    HBV cccDNAの制御と排除を目指す新規免疫治療薬の開発 平成24年度 総括・分担研究報告書, 2013  
  • 伊藤弘康, 安藤達也, 石川哲也, 清島満
    臨床病理, 61, 2013  
  • 伊藤弘康, 安藤量基, 石川哲也, 森脇久隆
    肝臓, 54(Supplement 3), 2013  
  • 伊藤弘康, 大瀧博文, 安藤達也, 安藤量基, 石川哲也, 森脇久隆, 清島満
    肝臓, 54(Supplement 1), 2013  
  • 仲本 賢太郎, 大橋 葉津希, 足立 真理子, 牛丸 星子, 宮崎 崇, 星 雅人, 稲垣 勇夫, 太田 浩敏, 古田 伸行, 竹村 正男, 和田 淳, 伊藤 弘康, 安田 満, 清島 満, 出口 隆
    臨床病理, 60(補冊) 209-209, Oct, 2012  
  • USHIMARU Seiko, INAGAKI Isao, ADACHI Mariko, HOSHI Masato, FURUTA Nobuyuki, TAKEMURA Masao, ITO Hiroyasu, SEISHIMA Mitsuru
    61(4) 736-740, Jul 25, 2012  
  • 林 麻実, 星 雅人, 牛丸 星子, 足立 真理子, 古田 伸行, 伊藤 弘康, 清島 満
    Sysmex Journal, 35(Suppl.1) 45-56, Jun, 2012  
  • 星 雅人, 足立 真理子, 林 麻実, 牛丸 星子, 稲垣 勇夫, 伊藤 弘康, 清島 満
    医学検査, 61(学会特集号) np290-np290, Apr, 2012  
  • 林 麻実, 星 雅人, 牛丸 星子, 足立 真理子, 古田 伸行, 伊藤 弘康, 清島 満
    医学検査, 61(学会特集号) np308-np308, Apr, 2012  
  • 星 雅人, 斉藤 邦明, 大瀧 博文, 大澤 陽介, 伊藤 弘康, 清島 満
    アミノ酸研究, 5(2) 113-114, Mar, 2012  
  • 大瀧 博文, 斉藤 邦明, 星 雅人, 大澤 陽介, 伊藤 弘康, 清島 満
    アミノ酸研究, 5(2) 114-115, Mar, 2012  
  • ADACHI Mariko, HOSHI Masato, USHIMARU Seiko, HATTORI Takayuki, HAYASHI Asami, INAGAKI Isao, ITO Hiroyasu, SEISHIMA Mitsuru
    61(1) 133-139, Jan 25, 2012  
  • 安藤達也, 大瀧博文, 伊藤弘康, 星雅人, 石川哲也, 斎藤邦明, 清島満
    臨床病理, 60, 2012  
  • HOSHI Masato, INOUE Rina, MIYAZAKI Takashi, OHTA Hirotoshi, TAKEMURA Masao, INAGAKI Isao, ITO Hiroyasu, SEISHIMA Mitsuru
    60(5) 741-745, Jul 25, 2011  
  • Tsuneo Watanabe, Tsuneo Watanabe, Tsuneo Watanabe, Hiroyasu Ito, Ayako Sekine, Ayako Sekine, Yuriko Katano, Yuriko Katano, Takashi Nishimura, Takashi Nishimura, Yoshihiro Kato, Jun Takeda, Mitsuru Seishima, Toshio Matsuoka
    Journal of Ultrasound in Medicine, 29(5) 697-708, May, 2010  
    Objective. Early detection of nerve dysfunction is important to provide appropriate care for patients with diabetic polyneuropathy. The aim of this study was to assess the echo intensity of the peripheral nerve and to evaluate the relationship between nerve conduction study results and sonographic findings in patients with type 2 diabetes mellitus. Methods. Thirty patients with type 2 diabetes (mean ± SD, 59.8 ± 10.2 years) and 32 healthy volunteers (mean, 53.7 ± 13.9 years) were enrolled in this study. The cross-sectional area (CSA) and echo intensity of the peripheral nerve were evaluated at the carpal tunnel and proximal to the wrist (wrist) of the median nerve and in the tibial nerve at the ankle. Results. There was a significant increase in the CSA and hypoechoic area of the nerve in diabetic patients compared with controls (wrist, 7.1 ± 2.0 mm2, 62.3% ± 3.0%; ankle, 8.9 ± 2.8 mm2, 57.6% ± 3.9%; and wrist, 9.8 ± 3.7 mm2, 72.3% ± 6.6%; ankle, 15.0 ± 6.1 mm2, 61.4% ± 5.3% in controls and diabetic patients, respectively; P < .05). Cross-sectional areas were negatively correlated with reduced motor nerve conduction velocity and delayed latency. Conclusions. These result
  • Japanese journal of clinical medicine, 68 46-49, Jan, 2010  
  • Ryo Tanaka, Masao Takemura, Masao Sato, Yasunori Yamada, Takahito Nakagawa, Takuro Horibe, Masato Hoshi, Hirofumi Otaki, Hiroyasu Ito, Mitsuru Seishima, Katsuji Shimizu
    Clinica Chimica Acta, 411(1-2) 22-25, Jan, 2010  
    Background: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are sensitive and highly specific markers for rheumatoid arthritis (RA). We evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme immunoassay (CLEIA) for anti-CCP antibodies, and compared it with that of ELISA. Methods: Ninety-nine RA patients who were diagnosed according to the American College of Rheumatology criteria, 16 patients with osteoarthritis, and 94 healthy subjects were included. Sera were used to assess the precision, functional sensitivity, and linearity of anti-CCP antibody determination by CLEIA and the correlation of anti-CCP antibody values between CLEIA and ELISA. Results: For anti-CCP antibodies by CLEIA, the total CV was 4.0 and 5.3% at 21.17 and 90 U/ml, respectively, and the lower limit of detection was 0.1 U/ml. The correlation of CLEIA (x) with ELISA (y) for anti-CCP was: y = 1.08x + 4.171, r = 0.9178 (p < 0.0001). No difference was observed in the sensitivity and specificity between CLEIA and ELISA. Conclusions: The automated CLEIA processing system for determining anti-CCP antibodies showed a good analytical performance, and suggested that the CLEIA system ha
  • Osawa Y, Seki E, Adachi M, Suetsugu A, Ito H, Moriwaki H, Seishima M, Nagaki M
    Hepatology, 51(1) 237-245, 2010  
  • 渡邉 恒夫, 伊藤 弘康, 松岡 敏男
    超音波techno, 21(6) 105-110, Nov, 2009  
  • Hirofumi Ohtaki, Kiyofumi Ohkusu, Haruki Sawamura, Hirotoshi Ohta, Rina Inoue, Junpei Iwasa, Hiroyasu Ito, Nobuo Murakami, Takayuki Ezaki, Hisataka Moriwaki, Mitsuru Seishima
    Journal of Clinical Microbiology, 47 3391-3393, Oct 1, 2009  
  • 石田 秀和, 星 雅人, 小池 紀子, 長屋 昌幸, 古田 伸行, 竹村 正男, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌, 34(4) 518-518, Sep, 2009  
  • 石田 秀和, 星 雅人, 小池 紀子, 長屋 昌幸, 古田 伸行, 竹村 正男, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌, 34(4) 564-564, Sep, 2009  
  • 足立 真理子, 服部 高幸, 星 雅人, 林 麻実, 牛丸 星子, 大橋 葉津希, 竹村 正男, 大澤 陽介, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌, 34(4) 671-671, Sep, 2009  
  • 星 雅人, 斉藤 邦明, 竹村 正男, 伊藤 弘康, 清島 満
    臨床化学, 38(Suppl.1) 145-145, Jul, 2009  
  • 古田 伸行, 太田 浩敏, 服部 高幸, 小池 紀子, 星 雅人, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 前田 悟司, 斉藤 邦明, 清島 満
    日本臨床検査自動化学会会誌, 34(3) 349-353, Jun, 2009  
  • 足立 真理子, 星 雅人, 服部 高幸, 小林 沙織, 牛丸 星子, 古田 伸行, 丸本 雅夫, 竹村 正男, 金森 寛光, 大澤 陽介, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌, 34(3) 365-370, Jun, 2009  
  • Tsuneo Watanabe, Tsuneo Watanabe, Hiroyasu Ito, Hiroyasu Ito, Ayako Morita, Yuriko Uno, Takashi Nishimura, Harumi Kawase, Yoshihiro Kato, Toshio Matsuoka, Jun Takeda, Mitsuru Seishima
    Journal of Ultrasound in Medicine, 28(6) 727-734, Jun, 2009  
    Objective. Diabetes mellitus is becoming a major cause of premature disability in Japan, and peripheral neuropathy is a common complication of diabetes. The aim of this study was to evaluate the relationship between the results of nerve conduction studies (NCS) and the size of the nerve determined by sonography in diabetic patients. Methods. Twenty diabetic patients (mean age ± SD, 57.1 ± 13.6 years) and 20 healthy volunteers (mean, 61.1 ± 8.9 years) were enrolled in this study. Patients' wrists that had symptoms of carpal tunnel syndrome were not included in the study; those that were included had negative Phalen test results. We then divided the patients into 2 groups (patients with and without diabetic symmetric polyneuropathy [DPN]). The cross-sectional area (CSA) was measured in the carpal tunnel 5 cm proximal to the wrist and elbow joint of the median nerve. Results. There was a significant increase in the CSA in patients with DPN in the carpal tunnel compared with the control participants (P < .01) and patients without DPN (P < .01). The CSA in the carpal tunnel showed a significant correlation with the motor nerve conduction velocity (r = -0.473). Conclusions. The CSA o
  • Yosuke Osawa, Masahito Nagaki, Hiroyasu Ito, Mitsuru Seishima, Hisataka Moriwaki
    GASTROENTEROLOGY, 136(5) A819-A819, May, 2009  
  • 小林 沙織, 星 雅人, 大橋 葉津希, 竹村 正男, 伊藤 弘康, 清島 満, 油野 友二
    日本腎臓学会誌, 51(3) 302-302, Apr, 2009  
  • 小林 沙織, 星 雅人, 稲垣 勇夫, 服部 高幸, 牛丸 星子, 大橋 葉津希, 古田 伸行, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 清島 満
    臨床病理, 57(3) 213-220, Mar, 2009  
    慢性腎臓病(CKD)における尿中の蛋白/クレアチニン比(P/C比)と尿沈渣の有用性を検討した。血清クレアチニンと尿検査の測定依頼のあった160検体について、アトラス試薬カートリッジPRO12によるP/C比(試験紙法)と各種生化学成分を比較した結果、試験紙法と定量法P/C比の相関は良好であり、P/C比の判定段階は腎機能障害を反映した妥当なものであった。また、試験紙法P/C比は従来の尿蛋白定性法より陽性率が高く、150mg/g・Cr群をカットオフ値とした場合の感度、特異度は良好で、300mg/g・Cr群の特異度は91.0%であった。一方、尿沈渣所見では病期の進行に伴って顆粒円柱やロウ様円柱などの多様な沈渣成分の増加を認め、硝子円柱は早期の腎障害を反映している可能性が示された。試験紙法P/C比と尿沈渣はCKDスクリーニングに有用である。
  • 星雅人, 斉藤邦明, 村上由希, 松本圭史, 有岡祐子, 田中領, 大澤陽介, 伊藤弘康, 松波英寿, 清島満
    アミノ酸研究, 2(2) 167-167, Jan, 2009  
  • 星 雅人, 古田 伸行, 小池 紀子, 太田 浩敏, 服部 高幸, 小林 沙織, 足立 真理子, 大橋 葉津希, 長屋 昌幸, 丸本 雅夫, 前田 悟司, 伊藤 弘康, 竹村 正男, 清島 満
    日本臨床検査自動化学会会誌, 33(5) 855-859, Nov, 2008  
  • Kaori Sudo, Yasuhiro Yamada, Kuniaki Saito, Kuniaki Saito, Syogo Shimizu, Hazuki Ohashi, Tomohiro Kato, Hisataka Moriwaki, Hiroyasu Ito, Mitsuru Seishima
    Biochimica et Biophysica Acta - Molecular Basis of Disease, 1782 671-679, Nov 1, 2008  
    In the present study, we used bone marrow transplanted mice and revealed the role of bone marrow derived cells in liver regeneration after partial hepatectomy (PH). Irradiated wild type (WT) mice received a bone marrow transplant from either WT, TNF (tumor necrosis factor)-α knockout (KO), or interleukin (IL)-6 KO donors. Both TNF-α KO- and IL-6 KO-transplanted mice compared with WT-transplanted mice showed decreased hepatocyte DNA synthesis after PH. TNF-α KO-transplanted mice showed no nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription (STAT) 3 binding after PH, while IL-6 KO-transplanted mice showed NF-κB, but not STAT3, binding. Lack of AP-1 or C/EBP binding or expression of c-jun or c-myc mRNA after PH was unrelated to the timing and amount of DNA replication. In conclusion, The TNF-α and IL-6 signals from the blood are necessary for liver regeneration and NF-κB and STAT3 binding are activated via TNF-α and IL-6 signal pathways. © 2008 Elsevier B.V. All rights reserved.
  • 牛丸 星子, 星 雅人, 服部 高幸, 小林 沙織, 信田 光明, 古田 伸行, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 清島 満
    医療と検査機器・試薬, 31(5) 569-574, Oct, 2008  
    新しいフィブリノゲン測定試薬として開発された「コアグピアFbg」の基本性能について、汎用の全自動血液凝固測定装置CA-7000を用いて検討した。その結果、再現性は良好であり、共存物質の影響は認めなかった。測定域は30〜600mg/dL付近まで認められ、試薬安定性については1ヵ月間は使用可能であった。オーレンベロナール緩衝液を用いた変法では、希釈直線性は得られるものの、従来法と比較すると低値に測定されており、専用の希釈液を用いるほうが良いと思われた。
  • 足立 真理子, 星 雅人, 服部 高幸, 小林 沙織, 牛丸 星子, 古田 伸行, 丸本 雅夫, 竹村 正男, 大澤 陽介, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌, 33(4) 671-671, Sep, 2008  
  • 吉川 武志, 原 武志, 鶴見 寿, 後藤 尚絵, 星 雅人, 伊藤 弘康, 北川 順一, 兼村 信宏, 笠原 千嗣, 竹村 正男, 清島 満, 森脇 久隆
    臨床血液, 49(9) 1176-1176, Sep, 2008  
  • 星 雅人, 斎藤 邦明, 高橋 健, 大山 正巳, 冨田 栄一, 竹村 正男, 伊藤 弘康, 清島 満
    臨床化学, 37(Suppl.1) 138-138, Aug, 2008  
  • Hiroyasu Ito, Hiroyasu Ito, Kazuki Ando, Kazuki Ando, Tetsuya Ishikawa, Toshinori Nakayama, Masaru Taniguchi, Kuniaki Saito, Kuniaki Saito, Michio Imawari, Hisataka Moriwaki, Takashi Yokochi, Shinichi Kakumu, Mitsuru Seishima
    International Immunology, 20 869-879, Jul 1, 2008  
    CTLs are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus (HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. In the present study, we found that alpha-galactosylceramide (α-GalCer), a ligand for Vα14-positive NKT cells, strongly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HBsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HBsAg or α-GalCer alone failed to induce HBsAg-specific CTLs, but they were induced by co-administration of both compounds. Furthermore, by limiting dilution analysis, we confirmed the existence of HBsAg-specific CTL precursors in the HBsAg transgenic mice immunized with HBsAg and α-GalCer. A blocking experiment using antibodies to cytokines and CD40 ligand showed that IL-2 and CD40-CD40L interaction mediate the enhancement of CTL induction caused by α-GalCer through NKT cell activation. Our results may open up a new method for clearing the virus from patients with persistent HBV infection. © The Japanese Society for Immunology. 2008. A
  • 小池 紀子, 古田 伸行, 服部 高幸, 星 雅人, 太田 浩敏, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 清島 満
    医療と検査機器・試薬, 31(1) 105-109, Feb, 2008  
    新しいシスタチンC測定試薬、FTラテックスシスタチンCについて基礎的性能評価を行った。日常検査としてクレアチニンクリアランス、尿素窒素およびクレアチニンを検査した150例を対象とした。日差再現性は良好な再現性を示した。ビリルビンF;18.1mg/dL、ビリルビンC;19.5mg/dL、溶血ヘモグロビン;490mg/dL、乳び;2290濁度、リウマチ因子;5001U/mLまで影響を認めなかった。有効測定範囲内での希釈直線性は良好であった。0.28〜0.41mg/L付近が実行検出限界濃度であった。腎・肝機能検査に異常を認めない男女99例で、性差は認めなかった。汎用機用の試薬との相関は、ネスコートGCシスタチン、イアトロCys-Cとは良好な相関を認めたが、N-ラテックスシスタチンCとイアトロCys-Cは、本法がやや高値傾向であった。Ccr(24時間)とは負、β2-ミクログロブリンとは正の相関が得られた。
  • 古田 伸行, 太田 浩敏, 服部 高幸, 小池 紀子, 星 雅人, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 前田 悟司, 斉藤 邦明, 清島 満
    日本臨床検査自動化学会会誌, 32(4) 605-605, Sep, 2007  
  • 内藤 智雄, 内木 隆文, 伊藤 弘康, 永木 正仁, 村上 啓雄, 森脇 久隆
    日本アフェレシス学会雑誌, 21 75-75, 2002  
  • Hiroyasu Ito, Mitsuru Seishima
    Journal of Biomedicine and Biotechnology, 2010  
    Cytotoxic T lymphocytes (CTLs) play a crucial role in the infections and the antitumor immunity. Induction and activation of antigen-specific CTLs is an important strategy in immunotherapy for various diseases, and several researchers have focused on the modulation of CTL induction and function. Natural killer T (NKT) cells are an important focus area of researchers studying immunomodulatory responses to tumors and infectious diseases. CD1d-restricted NKT cells consist of type I NKT cells and type II NKT cells. -galactosylceramide ( -GalCer)-activated type I NKT cells secrete both Th1 (e.g., IFN- ) and Th2 cytokines, affect the expression of costimulatory molecules in immune cells, and regulate the host immune system. Type II NKT cells, however, are stimulated by sulfatide, a self-glycolipid derived from myelin, and play an immunosuppressive role in animal model of autoimmune diseases. CTL generation, activation, and suppression are strongly affected by activated type I and type II NKT cells. Thus, the regulation of these NKT cells leads to the modification of CTL function. CTLs contribute to antimicrobial responses, antitumor immune and autoimmune responses. Understanding the role
  • Hirofumi Ohtaki, Hirofumi Ohtaki, Kiyofumi Ohkusu, Hirotoshi Ohta, Takashi Miyazaki, Jun Yonetamari, Taro Usui, Ichiro Mori, Hiroyasu Ito, Tatsuo Ishizuka, Mitsuru Seishima
    Journal of Infection and Chemotherapy, 19 1206-1209  
    A 91-year-old dog-owning woman with a history of hypertension and femoral neck fracture consulted our hospital with fever and femur pain with redness. Laboratory test results showed leukocytosis with 85 % neutrophils and high values of C-reactive protein and procalcitonin. In addition, growth of Gram-positive streptococcus was observed in two independent blood culture sets. The isolated bacterium was identified as Streptococcus canis on the basis of biochemical properties and sequencing analyses of the 16S rRNA gene. The patient recovered completely without critical illness following prompt antimicrobial treatment with ceftriaxone. S. canis, a β-hemolytic Lancefield group G streptococcus, is in general isolated from various animal sources, but its isolation from a human clinical sample is extremely rare. Since β-hemolytic streptococci can cause severe infectious diseases such as necrotizing fasciitis, it is absolutely necessary to start antimicrobial treatment immediately. It is necessary to identify pathogenic bacteria carefully and to obtain information on a patient's background, including history of contact with an animal, when S. canis is isolated. © 2013 Japanese Society o
  • Yosuke Osawa, Yosuke Osawa, Hiromitsu Kanamori, Ekihiro Seki, Masato Hoshi, Hirofumi Ohtaki, Yoichi Yasuda, Hiroyasu Ito, Atsushi Suetsugu, Masahito Nagaki, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima
    Journal of Biological Chemistry, 286 34800-34808  
    Nonalcoholic fatty liver disease is one of the most common liver diseases. L-Tryptophan and its metabolite serotonin are involved in hepatic lipid metabolism and inflammation. However, it is unclear whether L-tryptophan promotes hepatic steatosis. To explore this issue, we examined the role of L-tryptophan in mouse hepatic steatosis by using a high fat and high fructose diet (HFHFD) model. L-Tryptophan treatment in combination with an HFHFD exacerbated hepatic steatosis, expression of HNE-modified proteins, hydroxyproline content, and serum alanine aminotransaminase levels, whereas L-tryptophan alone did not result in these effects. We also found that L-tryptophan treatment increases serum serotonin levels. The introduction of adenoviral aromatic amino acid decarboxylase, which stimulates the serotonin synthesis from L-tryptophan, aggravated hepatic steatosis induced by the HFHFD. The fatty acid-induced accumulation of lipid was further increased by serotonin treatment in cultured hepatocytes. These results suggest that L-tryptophan increases the sensitivity to hepatic steatosis through serotonin production. Furthermore, L-tryptophan treatment, adenoviral AADC introduction, and ser
  • Masato Hoshi, Kuniaki Saito, Kuniaki Saito, Akira Hara, Ayako Taguchi, Hirofumi Ohtaki, Ryo Tanaka, Hidetsugu Fujigaki, Yosuke Osawa, Masao Takemura, Hidetoshi Matsunami, Hiroyasu Ito, Mitsuru Seishima
    Journal of Immunology, 185 3305-3312  
    Indoleamine 2,3-dioxygenase, the L-tryptophan-degrading enzyme, plays a key role in the powerful immunomodulatory effects on several different types of cells. Because modulation of IDO activities after viral infection may have great impact on disease progression, we investigated the role of IDO following infection with LP-BM5 murine leukemia virus. We found suppressed BM5 provirus copies and increased type I IFNs in the spleen from IDO knockout (IDO -/-) and 1-methyl-D-L-tryptophan-treated mice compared with those from wild-type (WT) mice. Additionally, the number of plasmacytoid dendritic cells in IDO-/- mice was higher in the former than in the WT mice. In addition, neutralization of type I IFNs in IDO-/- mice resulted in an increase in LP-BM5 viral replication. Moreover, the survival rate of IDO -/- mice or 1-methyl-D-L-tryptophan-treated mice infected with LP-BM5 alone or with both Toxoplasma gondii and LP-BM5 was clearly greater than the survival rate of WT mice. To our knowledge, the present study is the first report to observe suppressed virus replication with upregulated type I IFN in IDO-/- mice, suggesting that modulation of the IDO pathway may be an effective strategy fo
  • Masato Hoshi, Keishi Matsumoto, Hiroyasu Ito, Hirofumi Ohtaki, Yuko Arioka, Yosuke Osawa, Yasuko Yamamoto, Hidetoshi Matsunami, Akira Hara, Mitsuru Seishima, Kuniaki Saito
    Journal of Immunology, 188 3980-3987  
    The activity of IDO that catalyzes the degradation of tryptophan (Trp) into kynurenine (Kyn) increases after diseases caused by different infectious agents. Previously, we demonstrated that IDO has an important immunomodulatory function in immune-related diseases. However, the pathophysiological role of IDO following acute viral infection is not fully understood. To investigate the role of IDO in the L-Trp-Kyn pathway during acute viral myocarditis, mice were infected with encephalomyocarditis virus, which induces acute myocarditis. We used IDO-deficient (IDO -/-) mice and mice treated with 1-methyl-D,L-Trp (1-MT), an inhibitor of IDO, to study the importance of Trp-Kyn pathway metabolites. Postinfection with encephalomyocarditis virus infection, the serum levels of Kyn increased, whereas those of Trp decreased, and IDO activity increased in the spleen and heart. The survival rate of IDO -/- or 1-MT-treated mice was significantly greater than that of IDO +/+ mice. Indeed, the viral load was suppressed in the IDO -/- or 1-MT-treated mice. Furthermore, the levels of type I IFNs in IDO -/- mice and IDO -/- bone marrow-transplanted IDO +/+ mice were significantly higher than those in I
  • Hiroyasu Ito, Masato Hoshi, Hirofumi Ohtaki, Ayako Taguchi, Kazuki Ando, Kazuki Ando, Tetsuya Ishikawa, Yosuke Osawa, Akira Hara, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima
    Journal of Immunology, 185 4554-4560  
    IDO converts tryptophan to L-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, we examined the effect of IDO in α-galactosylceramide (α-GalCer)-induced hepatitis. The increase in IDO expression in the liver of wild-type (WT) mice administered α-GalCer was confirmed by real-time PCR, Western blotting, and IDO immunohistochemical analysis. The serum alanine aminotransferase levels in IDO-knockout (KO) mice after α-GalCer injection significantly increased compared with those in WT mice. 1-Methyl-D-tryptophan also exacerbated liver injury in this murine hepatitis model. In α-GalCer-induced hepatitis models, TNF-α is critical in the development of liver injury. The mRNA expression and protein level of TNF-α in the liver from IDO-KO mice were more enhanced compared with those in WT mice. The phenotypes of intrahepatic lymphocytes from WT mice and IDO-KO mice treated with α-GalCer were analyzed by flow cytometry, and the numbers of CD49b+ and CD11b+ cells were found to have increased in IDO-KO mice. Moreover, as a result of the increase in the number of NK cells and macrophages in the liver of IDO-KO mice in

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