Nano DDS-mediated cytokine delivery and control of allergic responses.

• Project/Area Number: 20390281
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MAZDA Osam Kyoto Prefectural University of Medicine, 医学研究科, 教授 (00271164)
• Co-Investigator(Kenkyū-buntansha): AKIYOSHI Kazunari 京都大学, 工学研究科, 教授 (90201285) ; 今西 二郎 京都府立医科大学, 医学研究科, 教授 (40112510)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2009: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2008: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
• Keywords: アレルギー / ぜんそく / ナノ材料 / アレルギー・ぜんそく / 内科 / 癌

Research Abstract

We explored the mechanisms underlying the IL-21-mediated suppression of IgE-based allergic responses. We also examined whether nano DDS is useful for therapeutic application for allergic diseases. Analyses of dose-response and administration methodology revealed that IL-21 may suppress allergic responses not only by inhibiting IgE class switch recombination but also by affecting other pathways. Then we asked whether IL-21 directly acts on mast cells. IL-21 signal suppresses degranulation of mast cell, while proliferation of mast cell precursors may be inhibited by Id2 transcriptional repressor. Meanwhile, nano DDS was also useful for desensitization procedures and significantly reduced IgE level while suppressing allergic responses. The present study may lead to a novel therapeutic strategy against allergic disorders.

Research Products

• [Journal Article] Interleukin-28B acts synergistically with cisplatin to suppress the growth of head and neck squamous cell carcinoma. (2011)
  • Author(s): Yoshimoto K, Kishida T, Nakano Hi, Matsui M, Shin-Ya M, Shimada T, Nakai S, Imanishi J, Takeuchi M, Hisa Y, Mazda O.
  • Journal Title: J Immunother 34(2) Pages: 139-148
  • Peer Reviewed
• [Journal Article] Intra-articular injection of hyaluronan restores the aberrant expression of matrix metalloproteinase-13 in osteoarthritic subchondral bone. (2011)
  • Author(s): Hiraoka N, Takahashi KA, Arai Y, Sakao K, Mazda O, Kishida T, Honjo K, Tanaka S, Kubo T.
  • Journal Title: J Orthop Ress Resrthop ResRessssRes 29(3) Pages: 354-360
  • Peer Reviewed
• [Journal Article] Interleukin-28B acts synergistically with cisplatin to suppress the growth of head and neck squamous cell carcinoma (2011)
  • Author(s): Yoshimoto K, et al.
  • Journal Title: J.Immunother. Volume: 34(2) Pages: 139-148
  • Peer Reviewed
• [Journal Article] Intra-articular injection of hyaluronan restores the aberrant expression of matrix meta Iloproteinase-13 in osteoarthritic subchondral bone (2011)
  • Author(s): Hiraoka N, et al.
  • Journal Title: J.Orthop.Res. Volume: 29(3) Pages: 354-360
  • Peer Reviewed
• [Journal Article] IL-21 Reduces Immediate Hypersensitivity Reactions in Mouse Skin by Suppressing Mast Cell Activation or IgE Production (2011)
  • Author(s): Tamagawa-Mineoka R, et al.
  • Journal Title: J.Invest.Dermatol. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Mitf silencing cooperates with IL-12 gene transfer to inhibit melanoma in mice. (2010)
  • Author(s): Nakai N, Kishida T, Hartmann G, Katoh N, Imanishi J, Kishimoto S, Mazda, O.
  • Journal Title: Int Immunopharmacol. 10(4) Pages: 540-545
  • Peer Reviewed
• [Journal Article] Early-stage blocking of Notch signaling inhibits the depletion of goblet cells in dextran sodium sulfate-induced colitis in mice. (2010)
  • Author(s): Shinoda M, Shin-Ya M, Naito Y, Kishida T, Ito R, Suzuki N, Yasuda H, Sakagami J, Imanishi J, Kataoka K, Mazda O, Yoshikawa T.
  • Journal Title: J. Gastroenterol 45(6) Pages: 608-617
  • NAID: 10027216548
  • Peer Reviewed
• [Journal Article] Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines. (2010)
  • Author(s): Nochi T, Yuki Y, Takahashi H, Sawada S, Mejima M, Kohda T, Harada N, Kong IG, Sato A, Kataoka N, Tokuhara D, Kurokawa S, Takahashi Y, Tsukada H, Kozaki S, Akiyoshi K, Kiyono H.
  • Journal Title: Nat Mater 9(7) Pages: 572-578
  • Peer Reviewed
• [Journal Article] Immunohistological analysis of peptide-induced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination. (2009)
  • Author(s): Nakai N, Katoh N, Germeraad WT, Kishida T, Ueda E, Takenaka H, Mazda O, Kishimoto S.
  • Journal Title: J. Dermatol. Sci 53(1) Pages: 40-47
  • Peer Reviewed
• [Journal Article] Comparison of anti-rheumatic effects of local RNAi-based therapy in collagen induced arthritis rats using various cytokine genes as molecular targets. (2009)
  • Author(s): Inoue A, Takahashi KA, Mazda O, Arai Y, Saito M, Kishida T, Shin-Ya M, Morihara T, Tonomura H, Sakao K, Imanishi J, Kubo T.
  • Journal Title: Mod Rheumatol 19(2) Pages: 125-133
  • NAID: 10025112341
  • Peer Reviewed
• [Journal Article] Osteoblasts derived from osteophytes produce inteleukin-6, interleukin-8 and matrix metalloproteinase-13 in osteoarthritis. (2009)
  • Author(s): Sakao, K., K.A. Takahashi, Y. Arai, M. Saito, K. Honjo, N. Hiraoka, H. Asada, M. Shin-Ya, J. Imanishi, O. Mazda, T. Kubo
  • Journal Title: J Bone Miner Metab 27(4) Pages: 412-423
  • Peer Reviewed
• [Journal Article] Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity. (2009)
  • Author(s): Matsui M, Kishida T, Nakano H, Yoshimoto K, Shin-Ya M, Shimada T, Nakai S, Imanishi J, Yoshimoto T, Hisa Y, Mazda O.
  • Journal Title: Cancer Res 69(6) Pages: 2523-2530
  • Peer Reviewed
• [Journal Article] Intracellular enzyme-responsive fragmentation of nonviral gene carriers leads to polyplex destabilization and enhanced transgene expression. (2009)
  • Author(s): Hashimoto T, Tachibana Y, Nozaki H, Mazda O, Niidome T, Murakami A, Yamaoka T.
  • Journal Title: Chemistry Lett 38(7) Pages: 718-719
  • Peer Reviewed
• [Journal Article] Raspberry-like assembly of cross-linked nanogels for protein delivery. (2009)
  • Author(s): Hasegawa U, Sawada SI, Shimizu T, Kishida T, Otsuji E, Mazda O, Akiyoshi K.
  • Journal Title: J Control Release 140(3) Pages: 312-317
  • Peer Reviewed
• [Journal Article] Raspberry-like assembly of cross-linked nanogels for protein delivery (2009)
  • Author(s): Hasegawa U, Sawada SI, Shimizu T, Kishida T, Otsuji E, Mazda O, Akiyoshi K.
  • Journal Title: J.Control.Release 140(3) Pages: 312-317
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Mazda O., Kishida T(分担執筆)
  • Journal Title: Front Biosci (Elite Ed). Molecular therapeutics of cancer by means of electroporation-based transfer of siRNAs and EBV-based expression vectors. PMID : 19482649(Albertson NY.) Pages: 316-331
• [Journal Article] Enhanced expression of interleukin-6, matrix metalloproteinase-13, and receptor activator of NF-kappaB ligand in cells derived from osteoarthritic subchondral bone. (2008)
  • Author(s): Sakao K, Takahashi KA, Mazda O, Arai Y, Tonomura H, Inoue A, Saito M, Fujioka M, Takamiya H, Imanishi J, Kubo T.
  • Journal Title: J Orthop Sci 13(3) Pages: 202-210
  • Peer Reviewed
• [Journal Article] Induction of chondrogenic phenotype in synovium-derived progenitor cells by intermittent hydrostatic pressure. (2008)
  • Author(s): Sakao K, Takahashi KA, Arai Y, Inoue A, Tonomura H, Saito M, Yamamoto T, Kanamura N, Imanishi J, Mazda O, Kubo T.
  • Journal Title: Osteoarthritis Cartilage 16(7) Pages: 805-814
  • Peer Reviewed
• [Journal Article] Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. (2008)
  • Author(s): Ito R, Kita M, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J, Imanishi J, Iwakura Y, Okanoue T, Yoshikawa T, Kataoka K, Mazda O.
  • Journal Title: Biochem Biophys Res Commun 377(1) Pages: 12-16
  • Peer Reviewed
• [Journal Article] Enhanced expression of interleukin-6, matrix metalloproteinase-13, and receptor activator of NF-kappaB ligand in cells derived from osteoarthritic subchondral bone (2008)
  • Author(s): Sakao K., et al.
  • Journal Title: J Orthop Sci. 13(3) Pages: 202-210
  • Peer Reviewed
• [Journal Article] Induction of chondrogenic phenotype in synovium-derivea progenitor cells by intermittent hydrostatic pressure (2008)
  • Author(s): Sakao K., et al.
  • Journal Title: Osteoarthritis Cartilage 16(7) Pages: 805-814
  • Peer Reviewed
• [Journal Article] Comparison of anti-rheumatic effects of local RNAi-based tnerapy in collagen induced arthritis rats using various cytokine genes as molecular targets (2008)
  • Author(s): Inoue A., et al.
  • Journal Title: Mod Rheumatol. 19(2) Pages: 125-133
  • Peer Reviewed
• [Journal Article] Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck suamous cell carcinoma through inducing antibody-dependent cellular cvtaoxiCitv (2008)
  • Author(s): Matsui M., et al.
  • Journal Title: Cancer Res. 69(6) Pages: 2523-2530
  • Peer Reviewed
• [Journal Article] Involvement of IL-17A in the pathogenesis of Dss-induced colitis in mice (2008)
  • Author(s): Ito R., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 377(1) Pages: 12-16
  • Peer Reviewed
• [Journal Article] Immunohistological analysis of peptide-induced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination (2008)
  • Author(s): Nakai N., et al.
  • Journal Title: J. Dermatol. Sci. 53(1) Pages: 40-47
  • Peer Reviewed
• [Journal Article] IL-21 Reduces Immediate Hypersensitivity Reactions in Mouse Skin by Suppressing Mast Cell Activation or IgE Production.
  • Author(s): Tamagawa-Mineoka R, Kishida T, Mazda O, Katoh N.
  • Journal Title: J Invest Dermatol in press
  • Peer Reviewed
• [Journal Article] Intracellular enzyme-responsive fragmentation of nonviral gene carriers leads to polyplex destabilization and enhanced transgene expression
  • Author(s): Hashimoto T, Tachibana Y, Nozaki H, Mazda O, Niidome T, Murakami A, Yamaoka T.
  • Journal Title: Chemistry Letters (in press)
  • Peer Reviewed
• [Journal Article] Mitf silencing cooperates with IL-12 gene transfer to inhibit melanoma in mice
  • Author(s): Nakai N, Kishida T, Hartmann G, Katoh N, Imanishi J, Kishimoto S, Mazda O.
  • Journal Title: Int. Immunopharmacol. (in press)
  • Peer Reviewed
• [Journal Article] Early-stage blocking of Notch signaling inhibits the depletion of goblet cells in dextran sodium sulfate-induced colitis in mice
  • Author(s): Shinoda M, Shin-Ya M, Naito Y, Kishida T, Ito R, Suzuki N, Yasuda H, Sakagami J, Imanishi J, Kataoka K, Mazda O, Yoshikawa T.
  • Journal Title: J.Gastroenterology (in press)
  • NAID: 10027216548
  • Peer Reviewed
• [Journal Article] Osteoblasts derived from osteophytes produce inteleukin-6, interleukin-8 and matrix metalloproteinase-13 in osteoarthritis
  • Author(s): Sakao K., et al.
  • Journal Title: Bone Miner Metab (in press)
  • Peer Reviewed
• [Presentation] タバコ主流煙による肺胞マクロファージのDNA 損傷とその修復 (2010)
  • Author(s): 廣野由里子、宮川真由子、佐倉正明、川添彩香、重吉瑛里、稲賀すみれ、松田修、長井苑子、竹内亨、Pinkerton KE、竹内実
  • Organizer: 日本アレルギー学会
  • Place of Presentation: 東京
• [Presentation] Gain-of-function and loss-of-function analyses in vivo of transcriptional factor and cytokine genes using Epstein-Barr virus-based episomal vectors, and their implication to novel strategies of gene therapy and regenerative medicine. (2010)
  • Author(s): Kishida T, Nakai N, Matsui M, Yoshimoto K, Nakano H, Shin-Ya M, Shimada T, Nakai S, Hisa Y, Katoh N, Mazda O.
  • Organizer: 2010International Symposium on Micro-Nano Mechatronics and Human Science (From Micro & Nano Scale Systems to Robotics & Mechatronics Systems)
  • Place of Presentation: Nagoya
• [Presentation] Cigarette Smoke Induces DNA Damage but not Apoptosis in Alveolar Macrophages. (2010)
  • Author(s): Hirono Y, Inoue S, Miyagawa M, Ishida T, Sakura M, Inaga S, Mazda O, Nagai S, Takeuchi T, Pinkerton KE, Takeuchi M.
  • Organizer: American Thoracic Society 2010 International Conference
  • Place of Presentation: New Orleans
• [Presentation] Gain-of-function and loss-of-function analyses in vivo of transcriptional factor and cytokine genes using Epstein-Barr virus-based episomal vectors, and their implication to novel strategies of gene therapy and regenerative medicine (2010)
  • Author(s): Mazda O, et al.
  • Organizer: 2010 International Symposium on Micro-Nano Mechatronics and Human Science
  • Place of Presentation: Nagoya
• [Presentation] IL-21 の多彩なin vivo 生理活性と分子病態制御への応用 (2009)
  • Author(s): 岸田綱郎、菅井学、清水章、今西二郎、横田義史、松田修
  • Organizer: 免疫カンファレンス
  • Place of Presentation: 京都
  • Year and Date: 2009-11-21
• [Presentation] IL-21の多彩なin vivo生理活性と分子病態制御への応用 (2009)
  • Author(s): 岸田綱郎、菅井学、清水章、今西二郎、横田義史、松田修
  • Organizer: 免疫カンファレンス
  • Place of Presentation: 京都
  • Year and Date: 2009-11-21
• [Presentation] Novel cytokine immunotherapy using IL-21 and IL-27 to control allergic and malignant disorders. (2009)
  • Author(s): Mazda O.
  • Organizer: 3rd Annual World Congress of Gene-2009
  • Place of Presentation: Foshan
• [Presentation] Nonviral gene administration by means of the Epstein-Barr virus (EBV)-based episomal vectors and it application to gene therapy and regenerative medicine (2009)
  • Author(s): Mazda O, Kishida T, Matsui M, Nakano H, Yoshimoto K, Shimada T, Nakai S, Imanishi J, Hisa Y.
  • Organizer: Proc.of the 2009 Int'l Symposium on Micro-NanoMechatronics and Human Science
  • Place of Presentation: Nagoya
• [Presentation] Novel cytokine immunotherapy using IL-21 and IL-27 to control allergic and malignant disorders (2009)
  • Author(s): Mazda O
  • Organizer: 3rd Annual World Congress of Gene-2009(招待講演)
  • Place of Presentation: Foshan, China
• [Presentation] IL-21 によるマウスにおけるアナフィラキシー抑制効果 (2008)
  • Author(s): 広村弥生、岸田綱郎、安田誠、濱雄光、松田修、久育男
  • Organizer: 第57回日本アレルギー学会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-28
• [Presentation] IL-21 の経鼻的投与によるアレルギー性鼻炎の抑制 (2008)
  • Author(s): 広村弥生、岸田綱郎、中野宏、濱雄光、松田修、久育男
  • Organizer: 第109回日本耳鼻咽喉科学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-05-16
• [Presentation] IL-21 administration into the nostril alleviates murine allergic rhinitis. (2008)
  • Author(s): Hiromura Y, Kishida T, Nakano H, Hama T, Mazda O, Hisa Y.
  • Organizer: The 12th Japan-Korean joint meeting of Otorhinolaryngology-Head and Neck Surgery.
  • Place of Presentation: Nara
  • Year and Date: 2008-03-05
• [Presentation] IL-21 はB 細胞にinhibitor of differentiation 2発現を誘導してアレルギーを抑制する (2008)
  • Author(s): 岸田綱郎、菅井学、清水章、今西二郎、横田義史、松田修
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 京都
• [Presentation] IL-21はB細胞にinhibitor of differentiation 2発現を誘導してアレルギーを抑制する (2008)
  • Author(s): 岸田綱郎, 他
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 京都
• [Book] Molecular therapeutics of cancer by means of electroporation-based transfer of siRNAs and EBV-based expression vectors. Front Biosci (Elite edition)1 (2009)
  • Author(s): Mazda O, Kishida, T.
• [Remarks]
  • URL: http://www.f.kpu-m.ac.jp/j/modules/pico/index.php?content_id=220