Identification of target protein(s) to abrogate chronic inflammation

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659404
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: NAKANO Hiroyasu 順天堂大学, 医学部, 准教授 (70276476)
• Project Period (FY): 2011 – 2012
• Keywords: TRAF2 / 腸炎 / インターロイキン 10 / TNFa / 好中球

Research Abstract

IL-10-secreting neutrophils accumulated in peripheral blood and bone marrow (BM) cells from Traf2-/- mice compared to wild-type mice. Treatment of Traf2-/- mice with neutralizing antibody against TNFa or crossing Traf2-/- mice with Tnfr1-/- mice reduced the percentages of IL-10-secreting neutrophils, suggesting that the development of IL-10-secreting neutrophils largely depended on TNFa signal. Finally, combined treatment of Traf2-/- mice with neutralizing antibodies against TNFa and IL-10, but not each antibody alone, substantially ameliorated colitis and prolonged survival. Together, abrogation of immunosuppressive conditions mediated by IL-10-secreting neutrophils might be an alternative strategy to treat chronic inflammatory diseases.

Research Products

• [Journal Article] Tumor Necrosis Factor Receptor Associated Factor 5 is an Essential Mediator of Ischemic Brain Infarction (2013)
  • Author(s): Wang, L., Y. Lu, H. Guan, D. Jiang, Y. Guan, X. Zhang, H. Nakano, Y. Zhou, Y. Zhang, L. Yang, and H. Li
  • Journal Title: J Neurochem
  • Peer Reviewed
• [Journal Article] Critical contribution of oxidative stress to TNFα-induced necroptosis downstream of RIPK1 activation (2013)
  • Author(s): Shindo, R., H. Kakehashi, K. Okumura, Y. Kumagai, and H. Nakano
  • Journal Title: Biochem Biophys Res Commun
  • Peer Reviewed
• [Journal Article] Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton (2013)
  • Author(s): Ly, D.L., F. Waheed, M. Lodyga, P. Speight, A. Masszi, H. Nakano, M. Hersom, S.F. Pedersen, K. Szaszi, and A. Kapus
  • Journal Title: Am J Physiol Cell Physiol Volume: 304 Pages: C115-127
  • Peer Reviewed
• [Journal Article] Shigella IpaH0722 E3 ubiquitin ligase effector targets TRAF2 to inhibit PKC-NF-kB activity in invaded epithelial cells (2013)
  • Author(s): Ashida, H., H. Nakano, and C. Sasakawa
  • Journal Title: PLoS Pathogens
  • Peer Reviewed
• [Journal Article] c-FLIP Maintains Tissue Homeostasis by Preventing Apoptosis and Programmed Necrosis (2012)
  • Author(s): Piao, X., S. Komazawa-Sakon, T. Nishina, M. Koike, J.H. Piao, H. Ehlken, H. Kurihara, M. Hara, N. Van Rooijen, G. Schutz, M. Ohmuraya, Y. Uchiyama, H. Yagita, K. Okumura, Y.W. He, and *H. Nakano
  • Journal Title: Sci Signal Volume: 5 Pages: 93
  • Peer Reviewed
• [Journal Article] Aberrant accumulation of interleukin-10-secreting neutrophils in TRAF2-deficient mice (2012)
  • Author(s): Piao, J.H., H. Yagita, K. Okumura, and *H. Nakano
  • Journal Title: Immunol Cell Biol Volume: 90 Pages: 881-888
  • Peer Reviewed
• [Journal Article] Interleukin-11 links oxidative stress and compensatory proliferation (2012)
  • Author(s): Nishina, T., S. Komazawa-Sakon, S. Yanaka, X. Piao, D.M. Zheng, J.H. Piao, Y. Kojima, S. Yamashina, E. Sano, T. Putoczki, T. DOI:, T. Ueno, J. Ezaki, H. Ushio, M. Ernst, K. Tsumoto, K. Okumura, and *H. Nakano
  • Journal Title: Sci Signal Volume: 5 Pages: 5
  • Peer Reviewed
• [Journal Article] Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice (2012)
  • Author(s): Minami, T., K. Kuwahara, Y. Nakagawa, M. Takaoka, H. Kinoshita, K. Nakao, Y. Kuwabara, Y. Y amada, C. Yamada, J. Shibata, S. Usami, S. Yasuno, T. Nishikimi, K. Ueshima, M. Sata, H. Nakano, T. Seno, Y. Kawahito, K. Sobue, A. Kimura, R. Nagai, and K. Nakao.
  • Journal Title: EMBO J Volume: 31 Pages: 4428-4440
  • Peer Reviewed
• [Journal Article] Crucial role for autophagy in degranulation of mast cells (2011)
  • Author(s): Ushio, H., T. Ueno, Y. Kojima, M. Komatsu, S. Tanaka, A. Yamamoto, Y. Ichimura, J. Ezaki, K. Nishida, S. Komazawa-Sakon, F. Niyonsaba, T. Ishii, T. Yanagawa, E. Kominami, H. Ogawa, K. Okumura, and *H. Nakano
  • Journal Title: J Allergy Clin Immunol Volume: 127 Pages: 1267-1276 e1266
  • Peer Reviewed
• [Journal Article] SHARPIN is a component of the NF-kB-activating linear ubiquitin chain assembly complex (2011)
  • Author(s): Tokunaga, F., T. Nakagawa, M. Nakahara, Y. Saeki, M. Taniguchi, S. Sakata, K. Tanaka, H. Nakano, and K. Iwai
  • Journal Title: Nature Volume: 471 Pages: 633-636
  • Peer Reviewed
• [Journal Article] Tumor Necrosis Factor Receptor-associated Factor (TRAF) 2 Controls Homeostasis of the Colon to Prevent Spontaneous Development of Murine Inflammatory Bowel Disease (2011)
  • Author(s): Piao, J.H., M. Hasegawa, B. Heissig, K. Hattori, K. Takeda, Y. Iwakura, K. Okumura, N. Inohara, and *H. Nakano
  • Journal Title: J Biol Chem Volume: 286 Pages: 17879-17888
  • Peer Reviewed
• [Journal Article] An unexpected role for autophagy in degranulation of mast cells (2011)
  • Author(s): *Nakano, H., and H. Ushio
  • Journal Title: Autophagy Volume: 7 Pages: 657-659
  • Peer Reviewed
• [Journal Article] Importin beta1 Protein-mediated Nuclear Localization of Death Receptor 5 (DR5) Limits DR5/Tumor Necrosis Factor(TNF)-related Apoptosis-inducing Ligand (TRAIL)-induced Cell Death of Human Tumor Cells (2011)
  • Author(s): Kojima, Y., M. Nakayama, T. Nishina, H. Nakano, M. Koyanagi, K. Takeda, K. Okumura, and H. Yagita
  • Journal Title: J Biol Chem Volume: 286 Pages: 43383-43393
  • Peer Reviewed
• [Journal Article] beta-catenin and Smad3 regulate the activity and stability of myocardin-related transcription factor during epithelial-myofibroblast transition (2011)
  • Author(s): Charbonney, E., P. Speight, A. Masszi, H. Nakano, and A. Kapus
  • Journal Title: Mol Biol Cell Volume: 22 Pages: 4472-4485
  • Peer Reviewed
• [Remarks] ホームページ
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/meneki/home.html