Understanding and manipulation of microtubule-mediated inflammatory response

• Project/Area Number: 25670027
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: SAITOH Tatsuya 大阪大学, 微生物病研究所, 准教授 (60456936)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 自然免疫 / 炎症 / サイトカイン / 微小管 / オルガネラ / マクロファージ / 翻訳後修飾

Outline of Final Research Achievements

Innate immune system is critically involved in induction of inflammatory responses. Innate immune system detects microbial components by pattern-recognition receptors and induces production of inflammatory cytokines. However, innate immune system also senses host-derived stimulatory factors and nutrient components, and often causes development of inflammatory diseases. We have examined a molecular mechanism underlying regulation of innate immune system and have revealed an essential role of microtubules in induction of inflammatory responses.

Research Products

• [Journal Article] Resveratrol inhibits the acetylated a-tubulin-mediated assembly of NLRP3-inflammasome. (2015)
  • Author(s): Misawa T*, Saitoh T*, Kozaki T, Park S, Lee H, Takahama M, Akira S (*Co-first authors).
  • Journal Title: Int Immunol Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of zinc-finger antiviral protein in host defense against Sindbis virus. (2015)
  • Author(s): Kozaki T, Takahama M, Misawa T, Matsuura Y, Akira S, Saitoh T* (*Corresponding author).
  • Journal Title: Int Immunol Volume: in press
  • Peer Reviewed
• [Journal Article] 5-azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival. (2015)
  • Author(s): Maruyama K, Fukasaka M, Uematsu S, Takeuchi O, Kondo T, Saitoh T, Martino M, Akira S.
  • Journal Title: J Biol Chem Volume: 290 Issue: 15 Pages: 9377-9386
  • DOI: 10.1074/jbc.m114.631374
  • Peer Reviewed / Open Access
• [Journal Article] The parasitophorous vacuole membrane of Toxoplasma gondii is targeted for disruption by ubiquitin-like conjugation systems of autophagy. (2014)
  • Author(s): Choi J, Park S, Biering SB, Selleck E, Liu CY, Zhang X, Fujita N, Saitoh T, Akira S, Yoshimori T, Sibley LD, Hwang S, Virgin HW.
  • Journal Title: Immunity. Volume: 40 Issue: 6 Pages: 924-35
  • DOI: 10.1016/j.immuni.2014.05.006
  • Peer Reviewed
• [Journal Article] Role of Mouse and Human Autophagy Proteins in IFN-γ-Induced Cell-Autonomous Responses against Thxoplasma gondii (2014)
  • Author(s): Jun Ohshima, Youngae Lee, Miwa Sasai, Tatsuya Saitoh, Ji Su Ma, Naganori Kamiyama, Yoshiharu Matsuura, Suh Pann-Ghill, Mikako Hayashi, Shigeyuki Ebisu, Kiyoshi Takeda, Shizuo Akira, and Masahiro Yamamoto.
  • Journal Title: The Journal of Immunology Volume: 192(7) Issue: 7 Pages: 3328-35
  • DOI: 10.4049/jimmunol.1302822
  • Peer Reviewed / Open Access
• [Journal Article] Innate immune response induced by baculovirus attenuates transgene expression in mammalian cells. (2014)
  • Author(s): Ono C., Ninomiya A., Yamamoto S., Abe T., Wen X., Fukuhara T., Sasai M., Yamamoto M., Saitoh T., Satoh T., Kawai T., Ishii J. K., Akira S., Okamoto T., and Matsuura Y.
  • Journal Title: Journal of Virology Volume: 88 Issue: 4 Pages: 2157-2167
  • DOI: 10.1128/jvi.03055-13
  • Peer Reviewed
• [Journal Article] Autophagy proteins control goblet cell function by potentiating reactive oxygen species production (2013)
  • Author(s): Patel KK, Miyoshi H, Beatty WL, Head RD, Malvin NP, Cadwell K, Guan JL, Saitoh T, Akira S, Seglen PO, Dinauer MC, Virgin HW, Stappenbeck TS
  • Journal Title: EMBO J Volume: 32 Issue: 24 Pages: 3130-3144
  • DOI: 10.1038/emboj.2013.233
  • Peer Reviewed
• [Journal Article] Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin (2013)
  • Author(s): Naonobu Fujita et al.
  • Journal Title: J. Cell Biol. Volume: 203 Issue: 1 Pages: 115-128
  • DOI: 10.1083/jcb.201304188
  • Peer Reviewed / Open Access
• [Journal Article] Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury (2013)
  • Author(s): Maejima I, Takahashi A, Omori H, Kimura T, Takabatake Y, Saitoh T, Yamamoto A, Hamasaki M, Noda T, Isaka Y, Yoshimori T
  • Journal Title: EMBO J. Volume: 32 Issue: 17 Pages: 2336-47
  • DOI: 10.1038/emboj.2013.171
  • Peer Reviewed / Open Access
• [Journal Article] Zinc-finger antiviral protein mediates retinoic acid inducible gene I-like receptor-independent antiviral response to murine leukemia virus. (2013)
  • Author(s): Hanna Lee, Jun Komano, Yasunori Saitoh, Shoji Yamaoka, Tatsuya Kozaki, Takuma Misawa, Michihiro Takahama, Takashi Satoh, Osamu Takeuchi, Naoki Yamamoto, Yoshiharu Matsuura, Tatsuya Saitoh. Shizuo Akira
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 110(30) Issue: 30 Pages: 12379-1284
  • DOI: 10.1073/pnas.1310604110
  • Peer Reviewed
• [Journal Article] Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. (2013)
  • Author(s): Takuma Misawa, Michihiro Takahama, Tatsuya Kozaki, Hanna Lee, Jian Zhou, Tatsuya Saitoh, Shizuo Akira
  • Journal Title: Nature Immunology Volume: 14(5) Issue: 5 Pages: 454-460
  • DOI: 10.1038/ni.2550
  • Peer Reviewed
• [Journal Article] Autophagy in infection, inflammation and immunity (2013)
  • Author(s): Deretic V, Saitoh T, Akira S
  • Journal Title: Nat Rev Immunol Volume: 13 Issue: 10 Pages: 722-737
  • DOI: 10.1038/nri3532
  • Peer Reviewed
• [Journal Article] Macrophages control innate inflammation. (2013)
  • Author(s): Shizuo Akira, Takuma Misawa, Takashi Satoh, Tatsuya Saitoh
  • Journal Title: Diabetes, Obesity and Metabolism Volume: 15 Issue: s3 Pages: 10-18
  • DOI: 10.1111/dom.12151
• [Journal Article] 自然免疫と痛風関節炎 (2013)
  • Author(s): 齊藤達哉、三澤拓馬、審良静男
  • Journal Title: 高尿酸血症と痛風 Volume: 21 Pages: 14-18
• [Journal Article] 微小管を介したミトコンドリアの局在変化はNLRP3インフラマソームの活性化を促進する (2013)
  • Author(s): 齊藤達哉、三澤拓馬、審良静男
  • Journal Title: 分子消化器病 Volume: 10 Pages: 99-102
• [Journal Article] オートファジーと炎症 (2013)
  • Author(s): 齊藤達哉
  • Journal Title: BIO Clinica Volume: 28 Pages: 23-26
• [Presentation] NLRP3インフラマソーム活性化を阻害する化合物の同定 (2015)
  • Author(s): 齊藤達哉，三澤拓馬，審良静男
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-20
• [Presentation] NLRP3インフラマソームを介した炎症応答の理解とその制御 (2014)
  • Author(s): 齊藤達哉
  • Organizer: 日本リウマチ学会 第1回アニュアルベーシックコースレクチャー
  • Place of Presentation: 東京
  • Year and Date: 2014-10-25
  • Invited
• [Presentation] 痛風発作の分子機構 (2014)
  • Author(s): 齊藤達哉
  • Organizer: 日本痛風・核酸代謝学会 第25回痛風研修会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-07
  • Invited
• [Presentation] NLRP3インフラマソームを介した炎症応答の理解とその制御 (2014)
  • Author(s): 齊藤達哉
  • Organizer: 第23回日本Cell Death学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-19
  • Invited
• [Presentation] NLRP3インフラマソームと炎症性疾患 (2014)
  • Author(s): 齊藤達哉
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-25
  • Invited
• [Presentation] 自然免疫応答の制御における細胞内分解系の役割
  • Author(s): 齊藤達哉
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] Regulation of innate immune response by autophagy
  • Author(s): Saitoh T
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International
  • Place of Presentation: Kyoto
  • Invited
• [Presentation] NLRP3インフラマソームの活性化に起因する痛風の発症
  • Author(s): 齊藤達哉
  • Organizer: 第47回日本痛風・核酸代謝学会総会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] Visualization of innate immune response occurring in cellular microcompartments
  • Author(s): Saitoh T
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張
  • Invited
• [Presentation] RNAウイルスに対する感染防御応答におけるZinc-finger antiviral proteinの役割
  • Author(s): 齊藤達哉、Lee Hanna、児崎達哉、三澤拓馬、高濱充寛、佐藤荘、竹内理、斉藤愛記、山岡昇司、山本直樹、松浦善治、駒野淳、審良静男
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] オートファジー関連因子による自然免疫の制御
  • Author(s): 齊藤達哉、審良静男
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 微小管を介したミトコンドリアの局在変化はNLRP3インフラマソームの活性化を促進する
  • Author(s): 齊藤達哉、三澤拓馬、審良静男
  • Organizer: 第22回日本Cell Death学会学術集会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 化合物ライブラリースクリーニングによるNLRP3インフラマソーム阻害剤の同定
  • Author(s): 齊藤達哉、三澤拓馬、審良静男
  • Organizer: 日本ケミカルバイオロジー学会第8回年会
  • Place of Presentation: 東京
• [Book] BIOLOGICAL DNA SENSOR, Chapter 4, Page 83-100. (2013)
  • Author(s): Saitoh T
  • Total Pages: 352
  • Publisher: Academic Press (Elsevier)
• [Remarks] 論文解説: Nat Immunol. 2013, 14, 454-460.
  • URL: http://shushoku-signal.com/result/23502856.html