Analysis of anti-tubercular activity through immune activation by polyphenol and consideration of its effectiveness to the prevention and the treatment

• Project/Area Number: 24501015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits, studies on eating habits
• Research Institution: Niigata University (2014); Sonoda Women's University (2012-2013)
• Principal Investigator: OZEKI Yuriko 新潟大学, 医歯学系, 助教 (00169301)
• Co-Investigator(Kenkyū-buntansha): OKA Mayuko 京都府立大学, 生命環境科学研究科(系), 准教授 (40347498) ; TAMARU Aki 大阪府立公衆衛生研究所, 感染症部, 研究員 (70270767)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ポリフェノール / 結核 / マクロファージ / マイクロアレー / 結核菌 / BCG

Outline of Final Research Achievements

Tuberculosis is the world's largest infectious disease. Because of its long administration period for the treatment, tuberculosis drugs with safer and fewer side effects are required. We found that kaempferol and luteolin inhibit growth of Mycobacterium tuberculosis infected in human monocyte-derived cell line THP1 at low cytotoxic level. In order to clarify the mechanism of inhibitory effect, we conducted microarray analysis. By the treatment of kaempferol, 41 genes affected growth inhibition of M. tuberculosis infected in THP1 cells.

Research Products

• [Journal Article] Direct detection of Mycobacterium avium in environmental water and scale samples by loop-mediated isothermal amplification. (2014)
  • Author(s): Nishiuchi Y, Tamaru A, Suzuki Y, Kitada S, Maekura R, Tateishi Y, Niki M, Ogura H, Matsumoto S.
  • Journal Title: J Water Health Volume: 12 Pages: 211-219
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 2.Intra-subspecies sequence variability of the MACPPE12 gene in Mycobacterium avium subsp. hominissuis. (2014)
  • Author(s): Iwamoto T, Arikawa K, Nakajima C, Nakanishi N, Nishiuchi Y, Yoshida S, Tamaru A,Tamura Y, Hoshino Y, Yoo H, Park YK, Saito H, Suzuki Y
  • Journal Title: Infection, Genetics and Evolution Volume: 21 Pages: 476-483
  • DOI: 10.1016/j.meegid.2013.08.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 私達の研究 結核ワクチン開発の現状と新しい結核ワクチン開発に向けて (2014)
  • Author(s): 松本壮吉、尾関百合子
  • Journal Title: 化学療法の領域 Volume: 30 Pages: 127-134
• [Journal Article] Hsc70 contributes to cancer cell survival by preventing RablA degradation under stress conditions (2014)
  • Author(s): Tanaka M, Mun S, Harada A, Ohkawa Y, Inagaki A, Sano S, Takahashi K, Izumi Y, Osada-Oka M, Wanibuchi H, Yamagata M, Yukimura T, Miura K, Shiota M, Iwao H.
  • Journal Title: PLoS One. Volume: 9
  • DOI: 10.1371/journal.pone.0096785
  • Peer Reviewed / Open Access
• [Journal Article] Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1 cells. (2014)
  • Author(s): Sano S, Izumi Y, Yamaguchi T, Yamazaki T, Tanaka M, Shiota M, Osada-Oka M, Nakamura Y, Wei M, Wanibuchi H, Iwao H, Yoshiyama M.
  • Journal Title: Biochem Biophys Res Commun Volume: 445 Pages: 327-33
  • DOI: 10.1016/j.bbrc.2014.01.183
  • Peer Reviewed
• [Journal Article] Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpGoligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG (2013)
  • Author(s): Taniguchi K, Takii T, Yamamoto S, Maeyama J, Iho S, Maruyama M, Iizuka N, Ozeki Y, Matsumoto S, Hasegawa T, Miyatake Y, Itoh S, Onozaki K.
  • Journal Title: Immun. Ageing Volume: 10 Pages: 25-25
  • DOI: 10.1186/1742-4933-10-25
  • Peer Reviewed
• [Journal Article] Tolvaptan attenuates left ventricular fibrosis after acute myocardial infarction in rats. (2013)
  • Author(s): Yamazaki T, Nakamura Y, Shiota M, Osada-Oka M, Fujiki H, Hanatani A, Shimada K, Miura K, Yoshiyama M, Iwao H, Izumi Y.
  • Journal Title: J Pharmacol Sci. Volume: 123 Pages: 58-66
  • Peer Reviewed
• [Journal Article] 複数自治体をまたぐ広域的結核分子疫学の基盤構築 ─ JATA（12）-VNTR型別に基づくクラスター形成とその傾向─ (2013)
  • Author(s): 和田崇之、田丸亜貴、岩本朋忠、有川健太郎、 中西典子、小向潤、松本健二、長谷篤
  • Journal Title: Kekkaku Volume: 88 Pages: 393-398
  • NAID: 10031162884
  • Peer Reviewed
• [Journal Article] JATA（12）-VNTR型別による結核集団発生事例の 菌株異同調査 (2013)
  • Author(s): 田丸亜貴、和田崇之、岩本朋忠、長谷篤
  • Journal Title: Kekkaku Volume: 88 Pages: 399-403
  • NAID: 10031162885
  • Peer Reviewed
• [Journal Article] Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis. (2013)
  • Author(s): Osada-Oka Mayuko
  • Journal Title: Microbiol Immunol Volume: 57 Pages: 30-37
  • DOI: 10.1111/j.1348-0421.2012.12005.x
  • Peer Reviewed
• [Journal Article] A simple multiplex PCR for the identification of Beijing family of Mycobacterium tuberculosis with a lineage-specific mutation in Rv0679c. (2013)
  • Author(s): Nakajima C, Tamaru A, Rahim Z, Poudel A, Maharjan B, Aye KS, Ling H, Hattori T, Iwamoto T, Fukushima Y, Suzuki H, Suzuki Y, Matsuba T
  • Journal Title: J Clin Microbiol. Volume: -
  • Peer Reviewed
• [Journal Article] 結核菌感染を診断するバイオマーカー (2012)
  • Author(s): 岡 真優子 尾関百合子 松本壮吉 岩尾 洋
  • Journal Title: 大阪市医学会雑誌 Volume: 61 Pages: 81-87
  • NAID: 40019589154
  • Peer Reviewed
• [Journal Article] Whole-genome sequence of the hypervirulent clinical strain Mycobacterium intracellulare M.i.198. (2012)
  • Author(s): Tateishi, Y., S. Kitada, K. Miki, R. Maekura, Y. Ogura, Y. Ozeki, Y. Nishiuchi, M. Niki, T. Hayashi, K. Hirata, K. Kobayashi, and S. Matsumoto.
  • Journal Title: J Bacteriol. Volume: 194 Pages: 6336-6336
  • DOI: 10.1128/jb.01439-12
  • Peer Reviewed
• [Journal Article] Dominant incidence of multidrug and exctensively drug-resistant specificMycobacterium tuberculosis clones in Osaka Prefecture, Japan. (2012)
  • Author(s): Tamaru, A., C. Nakajima, T. Wada, Y. Wang, M. Inoue, R. Kawahara, R. Maekura, Y. Ozeki, H. Ogura, K. Kobayashi, Y. Suzuki, and S. Matsumoto.
  • Journal Title: PLoS ONE Volume: 7
  • DOI: 10.1371/journal.pone.0042505
  • Peer Reviewed
• [Journal Article] A novel mechanism of growth phase-dependent tolerance to isoniazid in mycobacteria. (2012)
  • Author(s): Niki M, Niki M, Tateishi Y, Ozeki Y, Kirikae T, Lewin A, Inoue Y, Matsumoto M, Dahl JL, Ogura H, Kobayashi K, Matsumoto S
  • Journal Title: J Biol Chem. Volume: 287(33) Pages: 27743-27752
  • DOI: 10.1074/jbc.m111.333385
  • Peer Reviewed
• [Journal Article] 新しい結核ワクチン開発の展望 (2012)
  • Author(s): 松本壮吉、尾関百合子、小林和夫
  • Journal Title: 臨床と微生物 Volume: 39 Pages: 131-136
• [Journal Article] Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug resistance. (2012)
  • Author(s): Y.Suzuki, C.Nakajima, A Tamaru, H.Kim, et al
  • Journal Title: Int J Antimicrob Agents Volume: 39 Pages: 435-439
  • DOI: 10.1016/j.ijantimicag.2012.01.007
  • Peer Reviewed
• [Journal Article] Genetic diversity of Mycobacterium avium subsp. hominissuis strains isolated from humans, pigs, and human living environment. (2012)
  • Author(s): D Iwamoto T, Nakajima C, Nishiuchi Y, Kato T, Yoshida S, Nakanishi N, Tamaru A, Tamura Y, Suzuki Y, Nasu M
  • Journal Title: Infect Genet Evol. Volume: Vol.12 Pages: 846-52
  • DOI: 10.1016/j.meegid.2011.06.018
  • Peer Reviewed
• [Presentation] 高グルコースによる結核菌のNO抵抗性と増殖作用 (2015)
  • Author(s): 岡 真優子、大西 愛、石井 美菜子、尾関 百合子、松本 壮吉、三角 和広、 市川 寛、南山 幸子
  • Organizer: 第68回 日本酸化ストレス学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-06-11 – 2015-06-12
• [Presentation] The replication of intracellular mycobacteria under high concentration of glucose is independent of inducible nitric synthase expression (2015)
  • Author(s): Mayuko Osada-Oka, Yuriko Ozeki, Hiroshi Ichikawa, Yukiko Minamiyama, Sohkichi Matsumoto
  • Organizer: 12 th Asian Congress of Nutrition
  • Place of Presentation: Yokohama, Kanagawa
  • Year and Date: 2015-05-14 – 2015-05-18
• [Presentation] 当所における多剤耐性結核菌の発生状況と分子疫学：2007年以降とそれ以前の比較 (2015)
  • Author(s): 田丸亜貴
  • Organizer: 第90回日本結核学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2015-03-27 – 2015-03-28
• [Presentation] 成人の肺結核予防を目指した、新しい結核ワクチンの開発研究 (2014)
  • Author(s): 尾関百合子、西山晃史、松本壮吉
  • Organizer: 中部乳酸菌研究会
  • Place of Presentation: 長野
  • Year and Date: 2014-11-23
• [Presentation] コンタミネーションが原因の結核菌検査誤判定例とその対策に関する考察 (2014)
  • Author(s): 田丸亜貴
  • Organizer: 第73回日本公衆衛生学会総会
  • Place of Presentation: 宇都宮
  • Year and Date: 2014-11-05 – 2014-11-06
• [Presentation] Antigen 85A and mycobacterial DNA-binding protein 1 are targets of Immunoglobulin G in individuals with old tuberculosis in Japan (2014)
  • Author(s): Mayuko Osada-Oka, Yoshitaka Tateishi, Yuriko Ozeki, Seigo Kitada, Ryoji Maekura, and Sohkichi Matsumoto
  • Organizer: The 13 th Awaji International Forum on Infection and Immunity in Nara
  • Place of Presentation: Nara
  • Year and Date: 2014-09-08 – 2014-09-11
• [Presentation] ケニア共和国クワレ地区小学生を対象とした潜在性結核感染と寄生虫感染の関連 (2014)
  • Author(s): 尾関百合子、武田知芳里、岡部真裕子、井上学、岡真優子、平山幸雄、一瀬休生、小林和夫、松本壮吉
  • Organizer: 第８７回日本細菌学会総会
  • Place of Presentation: 東京都
• [Presentation] マクロファージの糖代謝酵素とグルコース濃度による結核菌の増殖抑制 (2014)
  • Author(s): 今川裕香子、岡真優子、尾関百合子、松本壮吉
  • Organizer: 第８７回日本細菌学会総会
  • Place of Presentation: 東京都
• [Presentation] M株の広域的分離の原因究明ー比較ゲノム解析に基づく「結核ゲノム疫学」の導入 (2014)
  • Author(s): 和田崇之、岩本朋忠、瀬戸順次、田丸亜貴、長谷篤、前田伸司、阿彦忠之、山本太郎
  • Organizer: 第８９回日本結核病学会総会
  • Place of Presentation: 岐阜県岐阜市
• [Presentation] リコンビナントBCG (rBCG)を用いた迅速スクリーニング法による抗結核薬の探索と同定 (2013)
  • Author(s): 尾関百合子 西内由紀子 小椋義俊 岩本朋忠 林哲也 岡真優子 仁木満美子 立石義隆 平山幸雄 松本壮吉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] 潜在性結核患者の血清中での結核菌抗原に対するイムノグロブリンｇ (2013)
  • Author(s): 岡真優子 立石義隆 平山幸雄 尾関百合子 小林和夫 松本壮吉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] 高病原性非結核性抗酸菌臨床分離株のゲノムシークエンス (2013)
  • Author(s): 立石義隆 平山幸雄 尾関百合子 西内由紀子 仁木満美子 小椋義俊 林哲也 小林和夫 松本壮吉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] ケニア共和国における学生の結核菌感染とhookworm感染の関連 (2013)
  • Author(s): 井上学 岡真優子 仁木満美子 尾関百合子 一瀬休生 小林和夫 松本壮吉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張メッセ（千葉）