Analysis of particulate-induced allergic responses

• Project/Area Number: 24591145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Osaka University
• Principal Investigator: Kuroda Etsushi 大阪大学, 免疫学フロンティア研究センター, 特任准教授 (10299604)
• Co-Investigator(Kenkyū-buntansha): 森本 泰夫 産業医科大学, 産業生態科学研究所, 教授 (30258628)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 粒子状物質 / アラム / シリカ / IgE / ダメージ関連分子パターン / マクロファージ / 脂質メディエーター / プロスタグランジン / Syk

Outline of Final Research Achievements

Recently, the number of patients suffering from allergic diseases has increased especially in developed countries, and many studies have demonstrated that particle pollutants and environmental particles such as diesel exhaust, sand dust and PM2.5 may exacerbate allergic responses mediated by type 2 immune responses. However, the mechanisms by which particulates elicit type 2 responses remain poorly understood.
Intratracheal instillation of particulates and OVA induced antigen-specific IgE responses. These responses were regulated by a MyD88 dependent and IL-1 signaling pathway. Particulates stimulated alveolar macrophages to induce cell death and IL-1α release both in vitro and in vivo. Our results suggest that DAMPs released by particulate exposure play an important role in IgE induction and inflammation.

Research Products

• [Journal Article] Hydroxypropyl-β-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen. (2015)
  • Author(s): Onishi M, Ozasa K, Kobiyama K, Ohata K, Kitano M, Taniguchi K, Homma T, Kobayashi M, Sato A, Katakai Y, Yasutomi Y, Wijaya E, Igarashi Y, Nakatsu N, Ise W, Inoue T, Yamada H, Vandenbon A, Standley DM, Kurosaki T, Coban C, Aoshi T, Kuroda E, Ishii KJ.
  • Journal Title: J Immunol. Volume: 194 Pages: 2673-2682
  • DOI: 10.4049/jimmunol.1402027
  • Peer Reviewed / Open Access
• [Journal Article] TLR9 and STING agonists synergistically induce innate and adaptive type-II IFN. (2015)
  • Author(s): Temizoz B, Kuroda E, Ohata K, Jounai N, Ozasa K, Kobiyama K, Aoshi T, Ishii KJ.
  • Journal Title: Europeal Journal of Immunology Volume: 45 Pages: 1159-1169
  • DOI: 10.1002/eji.201445132
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Significance of persistent inflammation in respiratory disorders induced by nanoparticles. (2014)
  • Author(s): Morimoto Y, Izumi H, Kuroda E.
  • Journal Title: Journal of Immunology Research Volume: 2014 Pages: 962871-962871
  • DOI: 10.1155/2014/962871
  • Peer Reviewed / Open Access
• [Journal Article] An ITAM-Syk-CARD9 signaling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells. (2014)
  • Author(s): Yasukawa. S., Miyazaki, Y., Yoshii, C., Nakaya, M., Ozaki, N., Toda, S., Kuroda, E., Ishibashi, K., Yasuda, T., Natsuaki, Y., Mi-ichi, F., Iizasa, E., Nakahara, T., Yamazaki, M., Kabashima, K., Iwakura, Y., Takai, T., Saito, T., Kurosaki, T., Malissen, B., Ohno, N., Furue, M., Yoshida, H., and Hara, H
  • Journal Title: Nat Commun. Volume: 5 Pages: 3755-3755
  • DOI: 10.1038/ncomms4755
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A non-agonistic Dectin-1 ligand transforms CpG into a multitask nano-particulate TLR9 agonist. (2014)
  • Author(s): Kobiyama K, Aoshi T, Narita H, Kuroda E, Hayashi M, Tetsutani K, Koyama S, Mochizuki S, Sakurai K, Katakai Y, Yasutomi Y, Saijo S, Iwakura Y, Akira S, Coban C, Ishii KJ.
  • Journal Title: Proc.Natl.Acad Sci. Volume: 111 Pages: 3086-3091
  • DOI: 10.1073/pnas.1319268111
  • Peer Reviewed
• [Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis. (2014)
  • Author(s): Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori M, Katsumata T, Arai S, Nakashima K, Kudo T, Kuroda E, Wu CH, Kao PH, Sakai M, Shimano H, Miyazaki T, Tontonz P, Takahashi S
  • Journal Title: Nature Comminications Volume: 5 Pages: 1-14
  • DOI: 10.1038/ncomms4147
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production. (2013)
  • Author(s): Sugita K, Ikenouchi-Sugita A, Nakayama Y, Yoshioka H, Nomura T, Sakabe J, Nakahigashi K, Kuroda E, Uematsu S, Nakamura J, Akira S, Nakamura M, Narumiya S, Miyachi Y, Tokura Y, Kabashima K
  • Journal Title: Scientific Reports Volume: 3 Pages: 2973-2973
  • DOI: 10.1038/srep02973
  • Peer Reviewed
• [Journal Article] Pulmonary toxicity of printer toner following inhalation and intratracheal instillation. (2013)
  • Author(s): Y. Morimoto, T. Oyabu, M. Horie, T. Kambara, H. Izumi, E. Kuroda, O. Creutzenberg, B. Bellmann, G. Pohlmann, S. Schuchardt, T. Hansen, H. Ernst
  • Journal Title: Inhalation Toxicology Volume: 12 Pages: 679-690
  • DOI: 10.3109/08958378.2013.835010
  • Peer Reviewed
• [Journal Article] D1-like dopamine receptors antagonist inhibits cutaneous immune reactions mediated by Th2 and mast cells. (2013)
  • Author(s): T. Mori, K. Kabashima, S. Fukamachi, E. Kuroda, J. Sakabe, M. Kobayashi, S. Nakajima, K. Nakano, Y. Tanaka, S. Matsushita, M. Nakamura, Y. Tokura
  • Journal Title: Journal of Dermatological Science Volume: 1 Pages: 112-116
  • DOI: 10.1016/j.jdermsci.2013.03.008
  • Peer Reviewed
• [Journal Article] ワクチンアジュバントの功罪と開発 (2013)
  • Author(s): 黒田悦史、石井健
  • Journal Title: 感染・炎症・免疫 Volume: 43 Pages: 74-77
• [Journal Article] 粒子アジュバントの生体への影響 ワクチンアジュバントからDAMPs、大気汚染物質まで (2013)
  • Author(s): 黒田悦史
  • Journal Title: 実験医学 Volume: 31 Pages: 34-40
• [Journal Article] Particulate adjuvant and innate immunity: past achievements, present findings, and future prospects. (2013)
  • Author(s): Kuroda E, Coban C, Ishii KJ
  • Journal Title: International Reviews of Immunology Volume: 32 Pages: 209-220
  • DOI: 10.3109/08830185.2013.773326
  • Peer Reviewed
• [Journal Article] 吸入性粒子状物質によるマクロファージの活性化とシグナル伝達経路の解析 (2013)
  • Author(s): 黒田悦史、堀江祐範、森本泰夫
  • Journal Title: 分子呼吸器病 Volume: 17 Pages: 149-151
• [Journal Article] 粒子アジュバントのメカニズム (2012)
  • Author(s): 黒田悦史
  • Journal Title: 実験医学（増刊） Volume: 30 Pages: 203-208
• [Journal Article] 粒子状物質によるTh2アジュバント効果 (2012)
  • Author(s): 黒田悦史
  • Journal Title: 臨床免疫・アレルギー科 Volume: 58 Pages: 171-177
• [Journal Article] アジュバントとしてのアルミニウム塩のTh2細胞誘導機構 (2012)
  • Author(s): 黒田悦史
  • Journal Title: 臨床免疫・アレルギー科 Volume: 58 Pages: 204-209
  • NAID: 40019419069
• [Presentation] 外来物質によるアレルギー性炎症のメカニズム (2015)
  • Author(s): 黒田悦史、石井健
  • Organizer: 日本衛生学会
  • Place of Presentation: 和歌山
  • Year and Date: 2015-03-26 – 2015-03-28
  • Invited
• [Presentation] Molecular mechanisms of particulate-induced pulmonary inflammation ~Intrinsic adjuvant and allergy~ (2015)
  • Author(s): Etsushi Kuroda
  • Organizer: Society of Toxicology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-03-22 – 2015-03-25
  • Invited
• [Presentation] 粒子状物質により誘導される肺特異的免疫反応 ～なぜ粒子状物質の吸入によりアレルギー性炎症が誘導されるのか？～ (2015)
  • Author(s): 黒田悦史、石井健
  • Organizer: 次世代アジュバント研究会
  • Place of Presentation: 大阪
  • Year and Date: 2015-01-20
• [Presentation] 粒子状物質の生体への影響 ～内因性アジュバント（DAMPs）とアレルギー～ (2014)
  • Author(s): 黒田悦史
  • Organizer: 第13回肺分子病態研究会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Particulate-induced systemic IgE production is mediated by DAMPs released from alveolar macrophages (2014)
  • Author(s): Etsushi Kuroda, Koji Ozasa, Koji Kobiyama and Ken J Ishii
  • Organizer: Cell Symposia Type 2 Immunity
  • Place of Presentation: Brugge, Belgium
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 粒子による内因性アジュバントの誘導とアレルギー性炎症 (2014)
  • Author(s): 黒田悦史、森本泰夫、石井健
  • Organizer: 日本毒性学会
  • Place of Presentation: 徳島
  • Year and Date: 2014-09-11 – 2014-09-12
• [Presentation] 粒子状物質の生体への影響 ～内因性アジュバント（DAMPs）とアレルギー～ (2014)
  • Author(s): 黒田悦史
  • Organizer: 日本毒性学会
  • Place of Presentation: 神戸
  • Year and Date: 2014-07-02 – 2014-07-04
  • Invited
• [Presentation] 粒子状物質により引き起こされる肺の炎症 ～DAMPsとアレルギー～ (2014)
  • Author(s): 黒田悦史、森本泰夫、石井健
  • Organizer: 肺サーファクタント分子病態研究会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-21
• [Presentation] 粒子状物質の生体への影響 ー内因性アジュバントとアレルギー性炎症－ (2014)
  • Author(s): 黒田悦史、石井健
  • Organizer: 日本インターフェロン・サイトカイン学会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-19 – 2014-06-20
• [Presentation] Particulate-induced systemic IgE production is mediated by DAMPs released from alveolar macrophages (2014)
  • Author(s): Etsushi Kuroda and Ken J Ishii
  • Organizer: マクロファージ分子細胞生物学国際シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2014-06-02 – 2014-06-03
• [Presentation] DMXAA, a vascular disruptive agent, is a potent inhibitor of prostaglandin synthesis. (2013)
  • Author(s): Etsushi Kuroda, Keiichi Ohata and Ken J Ishii
  • Organizer: The Joint International Meeting of The 78th Meeting of the Japanese Society of Interferon and Cytokine Research, The 21st International Symposium on Molecular Cell Biology of Macrophages 2013
  • Place of Presentation: 東京
• [Presentation] 粒子（アラム）アジュバント (2013)
  • Author(s): 黒田悦史
  • Organizer: 第２３回感染研シンポジウム 次世代型感染症ワクチンの戦略構想と展開 ―開発とレギュレーション－
  • Place of Presentation: 東京
  • Invited
• [Presentation] DMXAA, a vascular disruptive agent, is a potent inhibitor of prostaglandin synthesis (2013)
  • Author(s): Etsushi Kuroda, Keiichi Ohata and Ken J Ishii
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: イタリア ミラノ
• [Presentation] 粒子状物質により誘発される肺の炎症の解析 (2013)
  • Author(s): 黒田悦史
  • Organizer: 第20回日本免疫毒性学会
  • Place of Presentation: 東京
• [Presentation] Analysis of particulate-induced pulmonary allergic inflammation (2013)
  • Author(s): Etsushi Kuroda and Ken J Ishii
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Particulates control immune responses via the production of lipid mediators. (2012)
  • Author(s): Etsushi Kuroda
  • Organizer: 第８５回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Invited
• [Presentation] Particulates induce macrophage to produce lipid mediators via the Syk activation. (2012)
  • Author(s): Kuroda E, Ohata K, Coban C, Ishii JK
  • Organizer: 99th Annual Meeting of the The American Association of Immunologists
  • Place of Presentation: Hynes Convention Center (Boston)
• [Presentation] 吸入性粒子状物質によるマクロファージの活性化とシグナル伝達経路の解析
  • Author(s): 黒田悦史、堀江祐範、森本泰夫
  • Organizer: 第11回肺サーファクタント分子病態研究会
  • Place of Presentation: 札幌医科大学記念ホール（札幌）
• [Patent(Industrial Property Rights)] アレルギー誘発物質の検査、アレルギーの診断および治療 (2014)
  • Inventor(s): 石井健、黒田悦史
  • Industrial Property Rights Holder: 石井健、黒田悦史
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-111576
  • Filing Date: 2014-05-29
  • Application Year: 2014
• [Patent(Industrial Property Rights)] 異なる核酸アジュバントの組み合わせによる新規Th1誘導性アジュバントおよびその用途 (2014)
  • Inventor(s): 石井健、黒田悦史、Burcu temizoz
  • Industrial Property Rights Holder: 石井健、黒田悦史、Burcu temizoz
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-235934
  • Filing Date: 2014-11-20
  • Application Year: 2014