Exacerbation of colitis and promotion of colitis associated cancer by environmental chemicals via modulation of T cell mediated immunity

2011 Fiscal Year Final Research Report

• Project/Area Number: 21510067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Mie University
• Principal Investigator: KATO Takuma 三重大学, 大学院・医学系研究科, 准教授 (60224515)
• Project Period (FY): 2009 – 2011
• Keywords: 環境化学物質 / トリブチル錫 / 大腸炎症 / 大腸発がん / 酸化ストレス / Th1/Th2

Research Abstract

In the present study, the possible involvement of a prominent environmental chemical, tributyltin, in the exacerbation of colon inflammation and promotion colitis associated colorectal cancer was examined. Using a mouse model of azoxymethane and dexstran sodium salt induced colitis and colitis associated cancer, we found that exposure of an environmentally relevant dose of tributyltin exacerbated colon inflammation and promoted induction of colon cancer. We also found that the expression Th2 cytokines and downstream activation-induced cytidine deaminase that is know as natural mutator were significantly enhanced by tributyltin exposure before tumor emergence. On the other hand, mouse overexpressing intrinsic anti-oxidant, thioredoxin, was protected from the induction of colon cancer. Previously, we have shown that tributyltin promote Th2 cell differentiation that results in the enhancement of Th2 immunity through oxidative stress. Collectively, these results suggest that modulation of Th immunity by tributyltin that leads to the enhancement of AID expression is involved in the exacerbation of colon inflammation and promotion of colitis associated colorectal cancer.

Research Products

• [Journal Article] Intracellular Tumor-Associated Antigens Represent Effective Targets for Passive Immunotherapy (2012)
  • Author(s): Noguchi, T., T. Kato, L. Wang, Y. Maeda, H. Ikeda, E. Sato, A. Knuth, S. Gnjatic, G. Ritter, S. Sakaguchi, L. J. Old, H. Shiku, and H. Nishikawa
  • Journal Title: Cancer Res Volume: 72 Pages: 1672-1682
  • Peer Reviewed
• [Journal Article] UV irradiation of immunized mice induces type 1 regulatory T cells that suppress tumor antigen specific cytotoxic T lymphocyte responses (2011)
  • Author(s): Toda, M., L. Wang, S. Ogura, M. Torii, M. Kurachi, K. Kakimi, H. Nishikawa, K. Matsushima, H. Shiku, K. Kuribayashi, and T. Kato
  • Journal Title: Int J Cancer Volume: 129 Pages: 1126-1136
  • Peer Reviewed
• [Journal Article] Stat3-driven cancer-related inflammation as a key therapeutic target for cancer immunotherapy (2011)
  • Author(s): Kato, T
  • Journal Title: Immunotherapy Volume: 3 Pages: 587-590
  • Peer Reviewed
• [Journal Article] siRNA-mediated silencing of PD-1 ligands enhances tumor-specific human T-cell effector functions (2011)
  • Author(s): Iwamura, K., T. Kato, Y. Miyahara, H. Naota, J. Mineno, H. Ikeda, and H. Shiku
  • Pages: 185
  • DOI: doi:10.1038/gt.
  • Peer Reviewed
• [Journal Article] Thrombotic microangiopathy-like disorder after living-donor liver transplantation : A single-center experience in Japan (2011)
  • Author(s): Hori, T., T. Kaido, F. Oike, Y. Ogura, K. Ogawa, Y. Yonekawa, K. Hata, Y. Kawaguchi, M. Ueda, A. Mori, H. Segawa, K. Yurugi, Y. Takada, H. Egawa, A. Yoshizawa, T. Kato, K. Saito, L. Wang, M. Torii, F. Chen, A.-M. T. Baine, L. B. Gardner, and S. Uemoto
  • Journal Title: World J Gastroenterol Volume: 17 Pages: 1848-1857
  • Peer Reviewed
• [Journal Article] UV irradiation after immunization induces type 1 regulatory T cells that suppress Th2-type immune responses via secretion of IL-10 (2010)
  • Author(s): Wang, L., K. Saito, M. Toda, T. Hori, M. Torii, N. Ma, N. Katayama, H. Shiku, K. Kuribayashi, and T. Kato
  • Journal Title: Immunobiology Volume: 215 Pages: 124-132
  • Peer Reviewed
• [Journal Article] Pre-operative intracellular glutathione levels of peripheral monocytes as a biomarker to predict survival of colorectal cancer patients (2010)
  • Author(s): Uno, K., K. Okuno, T. Kato, S. Tada-Oikawa, N. Kan, H. Saotome, K. Yagi, and J. Hamuro
  • Journal Title: Cancer Immunol Immunother Volume: 59 Pages: 1457-1465
  • Peer Reviewed
• [Journal Article] Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation (2010)
  • Author(s): Torii, M., L. Wang, N. Ma, K. Saito, T. Hori, M. Sato-Ueshima, Y. Koyama, H. Nishikawa, N. Katayama, A. Mizoguchi, H. Shiku, J. Yodoi, K. Kuribayashi, and T. Kato
  • Journal Title: Eur J Immunol Volume: 40 Pages: 787-796
  • Peer Reviewed
• [Journal Article] Preferential induction of apoptosis in regulatory T cells by tributyltin : possible involvement in the exacerbation of allergic diseases (2010)
  • Author(s): Tada-Oikawa, S., M. Murata, and T. Kato
  • Journal Title: Nippon Eiseigaku Zasshi Volume: 65 Pages: 530-535
  • Peer Reviewed
• [Journal Article] Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells (2010)
  • Author(s): Muraoka, D., T. Kato, L. Wang, Y. Maeda, T. Noguchi, N. Harada, K. Takeda, H. Yagita, P. Guillaume, I. Luescher, L. J. Old, H. Shiku, and H. Nishikawa
  • Journal Title: J Immunol Volume: 185 Pages: 3768-3776
  • Peer Reviewed
• [Journal Article] Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals (2010)
  • Author(s): Mitsui, J., H. Nishikawa, D. Muraoka, L. Wang, T. Noguchi, E. Sato, S. Kondo, J. P. Allison, S. Sakaguchi, L. J. Old, T. Kato, and H. Shiku
  • Journal Title: Clin Cancer Res Volume: 16 Pages: 2781-2791
  • Peer Reviewed
• [Journal Article] Comprehensive and innovative techniques for liver transplantation in rats : a surgical guide (2010)
  • Author(s): Hori, T., J. H. Nguyen, X. Zhao, Y. Ogura, T. Hata, S. Yagi, F. Chen, A.-M. T. Baine, N. Ohashi, C. B. Eckman, A. R. Herdt, H. Egawa, Y. Takada, F. Oike, S. Sakamoto, M. Kasahara, K. Ogawa, K. Hata, T. Iida, Y. Yonekawa, L. Sibulesky, K. Kuribayashi, T. Kato, K. Saito, L. Wang, M. Torii, N. Sahara, N. Kamo, T. Sahara, M. Yasutomi, and S. Uemoto
  • Journal Title: World J Gastroenterol Volume: 16 Pages: 3120-3132
  • Peer Reviewed
• [Presentation] ヒト腫瘍抗原特異的T細胞へのPD-L1/PD-L2siRNA導入によるT細胞機能の増強 (2011)
  • Author(s): 岩村康一、加藤琢磨、宮原慶裕、直田浩明、峰野純一郎、岡本幸子、池田浩明、竹迫一任、珠玖洋
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20110630-0701
• [Presentation] Food contaminants that modulate immune responses leading to exacerbation of allergic diseases. (2011)
  • Author(s): Kato, T
  • Organizer: Opening ceremony and international symposium for Research Institute of Life and Pharmaceutical Sciences
  • Place of Presentation: Sunchon, Korea
  • Year and Date: 2011-10-27
• [Presentation] IL-17の発がん促進とがん免疫監視作用 (2011)
  • Author(s): 加藤琢磨
  • Organizer: 第20回日本癌病態治療研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-17
• [Presentation] 食品汚染物質トリブチルスズによるTh2型免疫応答誘導を介したアレルギー性疾患増悪作用 (2010)
  • Author(s): 及川(多田)佐枝子、川西正祐、村田真理子、加藤琢磨
  • Organizer: 第100回日本食品衛生学会学術講演会
  • Place of Presentation: 熊本
  • Year and Date: 2010-09-17
• [Presentation] Distinct roles of IL-17A in inflammation-induced tumor development and tumor immuno-sureveillance (2010)
  • Author(s): 加藤琢磨、西川博嘉、王立楠、鳥井美江、三井潤、前田優香、珠玖洋
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-27
• [Presentation] 抗CTLA-4抗体とがんワクチンの併用療法はステロイド抵抗性の完全な腫瘍の拒絶を誘発する (2010)
  • Author(s): 前田優香、西川博嘉、王立楠、村岡大輔、佐藤永一、加藤琢磨、坂口志文、珠玖洋
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-24
• [Presentation] IL-17の発がん促進と免疫監視作用 (2010)
  • Author(s): 加藤琢磨、西川博嘉、王立楠、鳥井美江、三井潤、前田優香、珠玖洋
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2010-07-22
• [Presentation] Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation (2010)
  • Author(s): Torii, M., Wang, L., Saito, K., Hori, T., Sato-Ueshima, M., Koyama, Y., Nishikawa, H., Katayama, N., Mizoguchi, A., Shiku, H., Yodoi, J., Kuribayashi, K., and Kato, T.
  • Organizer: Highest Award in Asthma Basic Mechanism in XXIX Congress of the European Academy of Allergy and Clinical Immunology
  • Place of Presentation: London, UK
  • Year and Date: 2010-06-08
• [Presentation] Effects of corticosteroids on tumor immunity induced by anti-CTLA-4 mAb therapy in a mouse model (2010)
  • Author(s): Maeda Y, Kato, T, Wang L, Muraoka D, Sato E, Wolchok JD, Old LJ, Shiku H, Nishikawa H
  • Organizer: American Association for Cancer Research 101^(st) Annual meeting
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2010-04-22
• [Presentation] Peptide vaccine induces apoptosis of antigen-specific CD8+ T cells (2010)
  • Author(s): Muraoka D, Nishikawa H, Kato T, Wang L, Maeda Y, Harada N, Noguchi T, Kawakami Y, Shiku H
  • Organizer: American Association for Cancer Research 101^<st> Annual meeting
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2010-04-21
• [Presentation] Distinct roles of IL-17A in inflammation-induced tumor development and tumor immunosurveillance (2009)
  • Author(s): Kato T, Nishikawa H, Wang L, Mitsui J, Maeda Y, Shiku H
  • Organizer: American Association for Cancer Research 101^<st> Annual meeting
  • Place of Presentation: New York, USA
  • Year and Date: 20090930-1002
• [Presentation] Environmental factors that affect human health and diseases (2009)
  • Author(s): Kato, T
  • Organizer: The BK21 Developmental Center of Anti-infective Organic Compounds of the Sunchon National University Workshop on Immunological Diseases
  • Place of Presentation: Suchon, Korea
  • Year and Date: 20090821-22
• [Presentation] Co-stimulatory moleculeの複合刺激による抗腫瘍免疫応答の増強 (2009)
  • Author(s): 西川博嘉、三井潤、王立楠、森和子、村岡大輔、山根真妃子、前田優香、加藤琢磨、珠玖洋
  • Organizer: 第13回日本がん免疫学会
  • Place of Presentation: 小倉
  • Year and Date: 20090624-25
• [Presentation] Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation (2009)
  • Author(s): 鳥井美江、王立楠、馬寧、斎藤佳菜子、堀智英、溝口明、珠玖洋、淀井淳二、栗林景容、加藤琢磨
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Distinct roles of Il-17A in inflammation-induced tumor development and tumor immuno-surveillance (2009)
  • Author(s): 加藤琢磨、西川博嘉、王立楠、三井潤、前田優香、珠玖洋
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Steroids rescue for autoimmune diseases induced after anti-CTLA-4 therapy breaks equilibrium state of anti-tumor responses (2009)
  • Author(s): 前田優香、西川博嘉、王立楠、村岡大輔、佐藤永一、加藤琢磨、坂口志文、珠玖洋
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Augmentation of immune responses by molecules of immuno-modulators provides outstanding anti-tumor capacity (2009)
  • Author(s): 王立楠、西川博嘉、三井潤、村岡大輔、前田優香、佐藤永一、近藤哲、加藤琢磨、珠玖洋
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Peptide vaccine elicits enhanced tumor growth associated with apoptosis of tumor antigen-specific CD8+ T cells (2009)
  • Author(s): 村岡大輔、西川博嘉、王立楠、前田優香、加藤琢磨、珠玖洋
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] メチルコラントレン誘発化学発がんにおけるIL-17Aの二面的役割 (2009)
  • Author(s): 加藤琢磨、西川博嘉、王立楠、三井潤、村岡大輔、前田優香、佐藤永一、近藤哲、珠玖洋
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] 免疫共刺激分子刺激による質的・量的免疫応答活性化による抗腫瘍免疫応答の増強 (2009)
  • Author(s): 王立楠、西川博嘉、三井潤、森和子、村岡大輔、前田優香、佐藤永一、近藤哲、加藤琢磨、珠玖洋
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] プチドワクチンによる抗原特異的CD8陽性T細胞のアポプトーシス (2009)
  • Author(s): 村岡大輔、西川博嘉、王立楠、前田優香、加藤琢磨、珠玖洋
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] ペプチドワクチンによる抗原特異的CD8陽性T細胞のアポプトーシス (2009)
  • Author(s): 西川博嘉、三井潤、王立楠、森和子、村岡大輔、山根真妃子、前田優香、加藤琢磨、珠玖洋
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] Inhibitory Effect of Steroids on anti-CTLA-4 mAb-Induced anti-tumor Response (2009)
  • Author(s): Noguchi T, Kato T, Muraoka D, Kondo S, Ritter G, Old LJ, Shiku H, Nishikawa H
  • Organizer: Cancer Immunology & Immunotherapy
  • Place of Presentation: New York, USA
  • Year and Date: 2009-10-02
• [Presentation] メチルコラントレン誘発化学発がんにおけるIL-17Aの二面的役割 (2009)
  • Author(s): 加藤琢磨,西川博嘉,王立楠,三井潤,前田優香,珠玖洋
  • Organizer: 第75回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-06-27
• [Book] UV-induce immune suppression that promotes skin cancer development and progression (2011)
  • Author(s): Kato, T., and L. Wang
  • Total Pages: 27-52