Activation mechanism and functional analysis of insect cytokine PP on innate immune response

• Project/Area Number: 21790063
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: HAMAMOTO Hiroshi The University of Tokyo, 大学院・薬学系研究科, 助教 (90361609)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自然免疫 / カイコ / 麻痺ペプチド / 昆虫サイトカイン / シグナル伝達 / 自然免疫応答 / サイトカイン / 細菌感染

Research Abstract

Insect cytokine PP (paralytic peptide) induce expression of genes for antimicrobial peptide via p38 MAPK pathway in fat body, and activate the phagocytic activity of hemocytes. Regarding the activation of PP, midgut has important role for recognition of cell wall components of bacteria and secret PP-activating factors. In this research, outline of function and activation mechanism of PP in innate immunity response was revealed.

Research Products

• [Journal Article] Purification of innate immunostimulant from green tea using a silkworm muscle contraction assay (2011)
  • Author(s): Dhital S, Hamamoto H, Urai M, Ishii K, Sekimizu K
  • Journal Title: Drug Discoveries and Therapeutics 5 Pages: 18-25
  • NAID: 130005054690
• [Journal Article] Purification of innate immunostimulant from green tea using a silkworm muscle contraction assay (2011)
  • Author(s): Dhital S, Hamamoto H, Urai M, Ishii K, Sekimizu K
  • Journal Title: Drug Discoveries and Therapeutics Volume: 5 Pages: 18-25
  • NAID: 130005054690
  • Peer Reviewed
• [Journal Article] Porphyromonas gingivalis peptidoglycans induce excessive activation of the innate immune system in silkworm larvae, (2010)
  • Author(s): Ishii K, Hamamoto H, Imamura K, Adachi T, Shoji M, Nakayama K, Sekimizu K
  • Journal Title: J Biol Chem 285 Pages: 33338-33347
• [Journal Article] The insect cytokine paralytic peptide (PP) induces cellular and humoral immune responses in the silkworm Bombyx mori, (2010)
  • Author(s): Ishii K, Hamamoto H, Kamimura M, Nakamura Y, Noda H, Imamura K, Mita K, Sekimizu K
  • Journal Title: J Biol Chem 285 Pages: 28635-28642
• [Journal Article] Porphyromonas gingivalis peptidoglycans induce excessive activation of the innate immune system in silkworm larvae. (2010)
  • Author(s): Ishii K, Hamamoto H, Imamura K, Adachi T, Shoji M, Nakayama K, Sekimizu K.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 33338-33347
  • Peer Reviewed
• [Journal Article] Insect cytokine paralytic peptide (PP) induces cellular and humoral immune responses in the silkworm Bombyx mori. (2010)
  • Author(s): Ishii K, Hamamoto H, Kamimura M, Nakamura Y, Noda H, Imamura K, Mita K, Sekimizu K.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 28635-28642
  • Peer Reviewed
• [Journal Article] Use of silkworms for identification of drug candidates having appropriate pharmacokinetics from plant sources. (2010)
  • Author(s): Asami Y, Horie R, Hamamoto H, Sekimizu K.
  • Journal Title: BMC Pharmacology Volume: 10 Pages: 7-7
  • Peer Reviewed
• [Journal Article] Use of silkworms for identification of drug candidates having appropriate pharmacokinetics from plant sources. (2010)
  • Author(s): Fujiyuki T, Imamura K, Hamamoto H, Sekimizu K
  • Journal Title: Drug Discoveries and Therapeutics Volume: 4 Pages: 349-354
  • Peer Reviewed
• [Journal Article] Silkworm as a model animal to evaluate drug candidate toxicity and metabolism (2009)
  • Author(s): Hamamoto H, Tonoike A, Narushima K, Horie R, Sekimizu K.
  • Journal Title: Comp Biochem Physiol C Toxicol Pharmacol 149 Pages: 334-339
  • Peer Reviewed
• [Journal Article] Hemocytes and humoral factors in silkworm blood are cooperatively involved in sheep erythrocyte aggregation
  • Author(s): Imamura K, Ishii K, Hamamoto H, Sekimizu K
  • Journal Title: Drug Discoveries and Therapeutics inpress
  • NAID: 130005054704
• [Presentation] カイコ細菌感染モデルを用いた治療効果を指標とした探索による、新規リポペプチド系抗生物質カイコシンの発見 (2011)
  • Author(s): 浜本洋、浦井誠、アトミカパウデル、堀江亮、村上和久、関水和久
  • Organizer: 日本薬学会第131年会(シンポジウム)
  • Place of Presentation: 静岡
• [Presentation] カイコ幼虫体液に存在する細胞増殖抑制因子の精製と機能解析 (2010)
  • Author(s): 安達達朗
  • Organizer: 第9回次世代を担う若手ファーマバイオフォーラム
  • Place of Presentation: 名古屋
  • Year and Date: 2010-10-02
• [Presentation] カイコ幼虫を用いた安全性試験・有効性試験 (2010)
  • Author(s): 浜本洋
  • Organizer: 日本実験代替法学会2010年講習会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-20
• [Presentation] カイコと哺乳動物におけるシトクロームP450代謝反応の共通性 (2010)
  • Author(s): 堀江亮、浜本洋、関水和久
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)
  • Year and Date: 2010-03-28
• [Presentation] Insect cytokine paralytic peptide activates innate immunity via nitric oxide production in Bombyx mori (2010)
  • Author(s): Kenichi Ishii, Hiroshi Hamamoto, Manabu Kamimura, Kazuhisa Sekimizu
  • Organizer: The 10th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路
• [Presentation] セラチア菌のO抗原によるカイコ血球細胞の細胞死誘導 (2010)
  • Author(s): 石井健一、臼井公人、今村亮俊、浜本洋、鈴木一史、渡邉剛志、関水和久
  • Organizer: 第32回日本分子生物学会・第83回日本生化学会大会合同年会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] Novel Therapeutically Effective Cyclic Lipopeptide Antibiotics Screened by Silkworm Infection Model (2010)
  • Author(s): H.HAMAMOTO, A.PAUDEL, M.URAI, R.HORIE, K.MURAKAMI, T.MOGI, K.SEKIMIZU
  • Organizer: 2010 Interscience Conference on Antimicrobial Agents and Chemotherapy
  • Place of Presentation: 米国、ボストン
• [Presentation] カイコにおけるシトクロームP450に関する研究 (2010)
  • Author(s): 浜本洋、堀江亮、関水和久
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会合同年会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] セラチア菌のO抗原によるカイコ血球細胞の細胞死誘導 (2010)
  • Author(s): 石井健一、臼井公人、今村亮俊、浜本洋、鈴木一史、渡邉剛志、関水和久
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会合同年会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] カイコにおいて昆虫サイトカイン paralytic peptide により誘導される自然免疫応答 (2009)
  • Author(s): 石井健一、浜本洋、神村学、中村有希、野田博明、三田和英、関水和久
  • Organizer: 第32回分子生物学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-10
• [Presentation] Establishment of novel bioassay system for screening the anti-infectious compounds using silkworm infection model (2009)
  • Author(s): Hiroshi Hamamoto, Ryo Horie, Atmika Paudel, Kazuhisa Murakami, Kazuhisa Sekimizu
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪大学(大阪府)
  • Year and Date: 2009-11-30
• [Presentation] カイコにおけるシトクロームP450代謝反応に関する研究 (2009)
  • Author(s): 堀江亮、浜本洋、関水和久
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] Metabolic reaction in silkworm by cytochrome P450 (2009)
  • Author(s): 堀江亮、浜本洋、関水和久
  • Organizer: 16th International Conference on Cytochrome P450
  • Place of Presentation: 万国津梁館(沖縄県)
  • Year and Date: 2009-06-22
• [Presentation] カイコにおいて昆虫サイトカインparalytic peptideにより誘導される自然免疫応答 (2009)
  • Author(s): 石井健一、浜本洋、神村学、中村有希、野田博明、三田和英、関水和久
  • Organizer: 第32回分子生物学会
  • Place of Presentation: 横浜
• [Remarks] ホームページ等
  • URL: http://www.f.u-tokyo.ac.jp/~bisei/research_hamamoto.html
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~bisei/research_hamamoto.html
• [Patent(Industrial Property Rights)] 植物体由来の自然免疫活性化作用が増強された自然免疫活性化組成物 (2009)
  • Inventor(s): 関水和久、浜本洋、小方康至
  • Industrial Property Rights Holder: 関水和久、浜本洋、小方康至
  • Filing Date: 2009-06-22
  • Overseas
• [Patent(Industrial Property Rights)] 自然免疫機構を活性化/抑制する作用を有する物質の評価方法及びスクリーニング方法、並びに、自然免疫機構を活性化/抑制するための薬剤、食品及びそれらの製造方法 (2008)
  • Inventor(s): 関水和久、浜本洋
  • Industrial Property Rights Holder: 関水和久、浜本洋
  • Industrial Property Number: 2009-509376
  • Filing Date: 2008-04-10
• [Patent(Industrial Property Rights)] 自然免疫機能活性化組成物の製造方法及び自然免疫機能活性化組成物 (2008)
  • Inventor(s): 関水和久、浜本洋
  • Industrial Property Rights Holder: 関水和久、浜本洋
  • Industrial Property Number: 2009-148108
  • Filing Date: 2008-07-02