Gene silencing of STAT6 with siRNA ameliorates contact hypersensitivity and allergic rhinitis

• Project/Area Number: 19591297
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YOKOZEKI Hiroo Tokyo Medical and Dental University, 医歯学総合研究科, 教授 (90210608)
• Co-Investigator(Kenkyū-buntansha): SATOH Takahiro 東京医科歯科大学, 医歯学総合研究科, 准教授 (30235361)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 皮膚炎症 / 再生学 / アレルギー性鼻炎 / サイトカイン / 干渉RNA / STAT6 / 核酸医薬 / ケモカイン / Th2 / 遺伝子療法 / アトピー性皮膚炎 / 接触皮膚炎 / TH2

Research Abstract

We established the gene therapy targeting for STAT6. We demonstrated that gene siliencing of STAT6 with siRNA ameliorates both contact hypersensitivity and allergic rhinitis by using model mouse.

Research Products

• [Journal Article] A therapeutic effect of STAT6 decoy oligodeoxynucleotide ointment in atopic dermatitis : a pilot study in adults (2009)
  • Author(s): Igawa K, Satoh T, Yokozeki H.
  • Journal Title: Br J Dermatol. 160(5) Pages: 1124-6
• [Journal Article] Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions : a potent therapeutic tool for Th1-and/or Th17-mediated skin inflammation (2009)
  • Author(s): Niwa H, Satoh T, Matsushima Y, Hosoya K, Saeki K, Niki T, Hirashima M, Yokozeki H.
  • Journal Title: Clin Immunol. 132(2) Pages: 184-94
• [Journal Article] Dental infection associated with nummular eczema as an overlooked focal infection (2009)
  • Author(s): Tanaka T, Satoh T, Yokozeki H.
  • Journal Title: J Dermatol. 36(8) Pages: 462-5
  • NAID: 10027064114
• [Journal Article] Basophils preferentially express mouse mast cell protease 11 among the mast cell tryptase family in contrast to mast cells (2009)
  • Author(s): Ugajin T, Kojima T, Mukai K, Obata K, Kawano Y, Minegishi Y, Eishi Y, Yokozeki H, Karasuyama H.
  • Journal Title: J Leukoc Biol. 18
• [Journal Article] A therapeutic effect of STAT6 decoy oligodeoxynucleotide ointment in atopic dermatitis : a pilot study in adults. (2009)
  • Author(s): Igawa K, et al
  • Journal Title: Br J Dermatol 160(5) Pages: 1124-6
  • Peer Reviewed
• [Journal Article] Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions : a potent therapeutic tool for Th1- and/or Th17-mediated skin inflammation (2009)
  • Author(s): Niwa H, et al
  • Journal Title: Clin Immunol 132(2) Pages: 184-94
  • Peer Reviewed
• [Journal Article] Therapeutic effects of interleukin-6 blockade in a murine model of polymyositis that does not require interleukin-17A (2009)
  • Author(s): Okiyama N, et al
  • Journal Title: Arthritis Rheum 60(8) Pages: 2505-12
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 横関博雄
  • Journal Title: EBMアレルギー疾患の治療:花粉症を合併した皮膚炎で注意すべき点は何か?(秋山一男ら編)(中外医学社) Pages: 318-321
• [Journal Article] CRTH2-dependent, STAT6-independent induction of cedar pollen dermatitis (2008)
  • Author(s): Oiwa M, Satoh T, Watanabe M, Niwa H, Hirai H, Nakamura M, Yokozeki H
  • Journal Title: Clin Exp Allergy 38(8) Pages: 1357-66
• [Journal Article] Increased expression of hematopoietic prostaglandin D synthase in CCR4-positive T cells from patients with atopic dermatitis (2008)
  • Author(s): Shimura C, Satho T, Yokozeki H
  • Journal Title: Acta Derm Venereol 88(5) Pages: 506-8
• [Journal Article] Overproduction of IgE induces macrophage-derived chemokine (CCL22) secretion from basophils (2008)
  • Author(s): Watanabe M, Satoh T, Yamamoto Y, Kanai Y, Karasuyama H, Yokozeki H.
  • Journal Title: J Immunol. 181(8) Pages: 5653-9
• [Journal Article] Transient macular erythema with eosinophilia in a patient carrying the FIP1L1-PDGFRA fusion gene (2008)
  • Author(s): Yahara H, Satoh T, Hashimoto T, Yokozeki H
  • Journal Title: Br J Dermatol 157(6) Pages: 1284-7
• [Journal Article] A de novo missense mutation in the keratin 13 gene in oral white sponge naevus (2008)
  • Author(s): Nishizawa A, Nakajima R, Nakano H, Sawamura D, Takayama K, Satoh T, Yokozeki H
  • Journal Title: Br J Dermatol 159(4) Pages: 422-3
• [Journal Article] 新しい皮膚科治療 核酸医薬とアトピー性皮膚炎 (2008)
  • Author(s): 横関博雄
  • Journal Title: 日皮会誌 118(13) Pages: 2892-4
• [Journal Article] 発症因子, 要因の除去による皮膚症状の改善と予防効果 (2008)
  • Author(s): 横関博雄
  • Journal Title: 皮膚の科学 7(sup10) Pages: 56-61
  • NAID: 130004725534
• [Journal Article] 【復活した好塩基球】好塩基球とは? 好塩基球の最新知見 (2008)
  • Author(s): 横関博雄
  • Journal Title: 皮膚アレルギーフロンテア 6(2) Pages: 85-90
• [Journal Article] 【免疫臓器としての皮膚】皮膚アレルギー疾患としてのアレルギー性接触皮膚炎) (2008)
  • Author(s): 横関博雄
  • Journal Title: アレルギー・免疫 15(4) Pages: 502-509
• [Journal Article] 皮膚疾患 アトピー性皮膚炎 (2008)
  • Author(s): 横関博雄
  • Journal Title: 病期・病態・重症度からみた疾患別看護過程(医学書院) Pages: 1558-1574
• [Journal Article] アトピー性皮膚炎, 湿疹 ; 接触皮膚炎, 湿疹, ステロイド薬が分かる本(宮坂信之編) (2008)
  • Author(s): 横関博雄
  • Journal Title: 法研 Pages: 140-153
• [Journal Article] 皮膚疾患、皮膚疾患の診断学 (2008)
  • Author(s): 横関博雄
  • Journal Title: 臨床病態学(杉浦雅人編)(医歯薬出版) Pages: 306-312
• [Journal Article] Overproduction of IhE indueved macrophage-derived chemokine (CCL22) secretion from basophi1 (2008)
  • Author(s): Watanabe M, Satoh T, et al
  • Journal Title: J Immunol 15 Pages: 5653-5659
  • Peer Reviewed
• [Journal Article] CRTH2-dependent, STAT6-independent induction of cedar polien dermatitis. (2008)
  • Author(s): Oiwa M, Satoh T, Watanabe M, et al
  • Journal Title: Clin Exp Allergy 38(8) Pages: 1357-66
  • Peer Reviewed
• [Journal Article] Increased Expression of Hematopotetic Prostaglandin D Synthasein CCR4-positive T Cells From Patients with Atopic Dermatitis. (2008)
  • Author(s): Shimura C, Satoh T, Yokozeki H
  • Journal Title: Acta Derm Venereol 88(5) Pages: 506-8
  • Peer Reviewed
• [Journal Article] Odontogenic focal infection could be partly involved in the pathogenesis of atopic dermatitis as exacerbating factor (2007)
  • Author(s): Igawa K, Nisioka K, Yokozeki H
  • Journal Title: Int J Dermatol 46(4) Pages: 376-9
• [Journal Article] Airborne contact dermatitis due to Japanese cedar pollen (2007)
  • Author(s): Yokozeki H, Satoh T, Katayama I, Nishioka K
  • Journal Title: Contact Dermatitis 56(4) Pages: 224-8
• [Journal Article] スギ花粉性皮膚炎 (2007)
  • Author(s): 横関博雄
  • Journal Title: 綜合臨牀 56(3) Pages: 627-629
• [Journal Article] Odontogenic focal infection could be partly involved in the pathogenesis of atopic dermatitis as exacerbating factor. (2007)
  • Author(s): Igawa K, Nishioka K, Yokozeki H.
  • Journal Title: Int J Dermatol 464(4) Pages: 376-379
  • Peer Reviewed
• [Journal Article] Airborne contact dermatitis due to Japanese cedar pollen. (2007)
  • Author(s): Yokozeki H, Satoh T, Katayama I, Nishioka K.
  • Journal Title: Contact Dermatitis, 56(4) Pages: 224-8
  • Peer Reviewed
• [Journal Article] Transient macular erythema with eosinophilia in a patient carrying the FIP1L1-PDGFRA fusion gene. (2007)
  • Author(s): Yahara H, Satoh T, Hashimoto T. Yokozeki H.
  • Journal Title: Br J Dermatol. 157(6) Pages: 1284-7
  • Peer Reviewed
• [Presentation] 接触皮膚炎診療ガイドラインの概説 (2009)
  • Author(s): 横関博雄、高山かおる
  • Organizer: 第108回日本皮膚科学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2009-04-25
• [Presentation] Therapeutic potential of STAT6 siRNA in contact hypersensitivity (2008)
  • Author(s): Hosoya K, Satoh T, Yokozeki H
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] Therapeutic potential of STAT6 siRNA in contacthypersensitivity (2008)
  • Author(s): Hosoya K, et al
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-01
• [Presentation] Basophils involved in cutaneous allergic responses, detected by newly established mAbbs specific to basophil granular enzymes mMCP-8 and mMCP-11 (2008)
  • Author(s): Ugajin T, Kojima T, Obata K, Tsujimura Y, Mukai K, Kawano Y Satoh T, Minegishi Y, Yokozeki H, Karasuyama H
  • Organizer: 第5回国際研究皮膚科学会(IID)
  • Place of Presentation: 京都
  • Year and Date: 2008-05-17
• [Presentation] Deficiency of PGD2 receptors, DP and CRTH2, enhances contact hypersensitivity (2008)
  • Author(s): Otani S, Satoh T, Yamamoto Y, Hirai H, Narumiya S, Yokozeki H, Nakamura M
  • Organizer: 第5回国際研究皮膚科学会 (IID)
  • Place of Presentation: 京都
  • Year and Date: 2008-05-15
• [Presentation] The atable form of galectin-9, a ligand for Tim-3, as a novel therapeutic tool for Th1-and/or Th17-mediated skin inflammation (2008)
  • Author(s): Niwa H, Satoh T ,Hosoya K, Hirashima M, Yokozeki H
  • Organizer: 第5回国際研究皮膚科学会 (IID)
  • Place of Presentation: 京都
  • Year and Date: 2008-05-15
• [Presentation] Treatment of the allergic cutaneous inflammation in mouse model by STAT6 inhibition with RNA (2008)
  • Author(s): Hosoya K, Igawa K, Satoh T, Yokozeki H
  • Organizer: 第5回国際研究皮膚科学会 (IID)
  • Place of Presentation: 京都
  • Year and Date: 2008-05-15
• [Presentation] A therapeutic effect of STAT6 decoy oligodeoxynucleotides ointment in atopic dermatitis 5th Georg Rajka International Symposium on Atopic Dermatitis (2008)
  • Author(s): Igawa K, Satoh T, Yokozeki H
  • Place of Presentation: 京都
  • Year and Date: 2008-05-13
• [Presentation] CRTH2-dependent, STAT6-independent induction of cedar pollen dermatitis (2008)
  • Author(s): Watanabe M, Satoh T, Oiwa M, Niwa H, Nakamura M, Yokozeki H
  • Organizer: International Investigative Dermatology (IID)
  • Place of Presentation: Kyoto
• [Presentation] Cutaneous manifestations of Oriental patients with dermatomyositis and the seborrheic pattern of facial eryhtema (2007)
  • Author(s): H. Yokozeki, N. Okiyama, et. al.
  • Organizer: 21th World Congress
  • Place of Presentation: Buenos Aires
  • Year and Date: 2007-10-01
• [Presentation] A therapeutic effect of STAT6 decoy oligodeoxynuckeoties ointment in atopic dermatitis
  • Author(s): Igawa K, Yahara H, Kanai Y, Sumi K, Satoh T, Nishioka K, Yokozeki H
  • Organizer: 36th Annual European
• [Presentation] A therapeutic effect of STAT6 decoy oligodeoxynuckeoties ointment in atopic dermatitis
  • Author(s): Igawa K, Yahara H, Kanai Y, Sumi K, Satoh T, Nishioka K, Yokozeki H
  • Organizer: 36th Annual European
• [Book] ステロイド薬がわかる本 : 皮膚科(宮坂信之編) (2008)
  • Author(s): 横関博雄
  • Publisher: 法研
• [Book] 蕁麻疹 ガイドライン:外来診療2007 (2007)
  • Author(s): 横関博雄
  • Publisher: 医薬ジャーナル社
• [Remarks] ホームページ等
• [Patent(Industrial Property Rights)] アレルギー疾患の治療のための核酸医薬 (2009)
  • Inventor(s): 横関博雄, 細矢一輝, 佐藤貴浩, ハプロファーマ
  • Industrial Property Rights Holder: 横関博雄, 細矢一輝, 佐藤貴浩, ハプロファーマ
  • Filing Date: 2009-03-12
  • Overseas
• [Patent(Industrial Property Rights)] アレルギー疾患の治療のための核酸医薬 (2009)
  • Inventor(s): 横関博雄
  • Industrial Property Rights Holder: 横関博雄
  • Filing Date: 2009-04-08
  • Overseas
• [Patent(Industrial Property Rights)] アレルギー疾患の有効な核酸医薬 (2008)
  • Inventor(s): 横関博雄, 細矢一輝, 佐藤貴浩, ハプロファーマ
  • Industrial Property Rights Holder: 横関博雄, 細矢一輝, 佐藤貴浩, ハプロファーマ
  • Industrial Property Number: 2008-237007
  • Filing Date: 2008-10-14
• [Patent(Industrial Property Rights)] アレルギー疾患に有効な核酸医薬 (2008)
  • Inventor(s): 横関博雄根本靖久
  • Industrial Property Rights Holder: 横関博雄根本靖久
  • Filing Date: 2008-08-13