Analysis of Molecular Pathogenesis of Allergy and Pulmonary Inflammation by CFTR Deficiency and its Therapeutic Application

• Project/Area Number: 21790083
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: SHUTO Tsuyoshi Kumamoto University, 大学院・生命科学研究部, 講師 (80333524)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 薬理学 / 分子生物学 / CFTR / NGF / 表皮 / アレルギー / 炎症 / ダニ抗原 / 掻痒 / TLR2 / セリンプロテアーゼ

Research Abstract

We sought to understand the mechanisms responsible for the phenotype of allergy and pulmonary inflammation by CFTR deficiency. Although we found the serine protease-dependent production of 25kDa fragment derived from mutated CFTR, the fragment did not seem to be involved in the regulation of TLR2 gene expression. We further concluded that CFTR in keratinocytes plays a critical role for the regulation of peripheral nerve function and pruritus sensation.

Research Products

• [Journal Article] Lucidenic acids-rich extract from antlered form of Ganoderma lucidum enhances TNFalpha induction in THP-1 monocytic cells possibly via its modulation of MAP kinases p38 and JNK. (2011)
  • Author(s): Watanabe, K., T.Shuto, M.Sato, K.Onuki, S.Mizunoe, S.Suzuki, T.Sato, T.Koga, M.A.Suico, H.Kai, T.Ikeda.
  • Journal Title: Biochem Biophys Res Commun 408 Pages: 18-24
  • Peer Reviewed
• [Journal Article] Posttranslational negative regulation of glycosylated and non-glycosylated BCRP expression by Derlin-1. (2011)
  • Author(s): Sugiyama, T., T.Shuto, S.Suzuki, T.Sato, T.Koga, M.A.Suico, H.Kusuhara, Y.Sugiyama, D.M.Cyr, H.Kai.
  • Journal Title: Biochem Biophys Res Commun 404 Pages: 853-858
  • Peer Reviewed
• [Journal Article] CFTR-deficiency renders mice highly susceptible to cutaneous symptoms during mite infestation. (2011)
  • Author(s): Hashimoto, Y., T.Shuto, S.Mizunoe, A.Tomita, T.Koga, T.Sato, M.Takeya, M.A.Suico, A.Niibori, T.Sugahara, S.Shimasaki, T.Sugiyama, B.Scholte,H.Kai.
  • Journal Title: Lab Invest 91 Pages: 509-518
  • Peer Reviewed
• [Journal Article] Posttranslational negative regulation of glycosylated and non-glycosylated BCRP expression by Derlin-1. (2011)
  • Author(s): Sugiyama T, et al.
  • Journal Title: Biochem Biophys Res Commun. Volume: 404(3) Pages: 853-858
  • Peer Reviewed
• [Journal Article] Curcumin decreases toll-like receptor-2 gene expression and function in human monocytes and neutrophils. (2010)
  • Author(s): Shuto, T., T.Ono, Y.Ohira, S.Shimasaki, S.Mizunoe, K.Watanabe, M.A.Suico, T. Koga, T.Sato, S.Morino, K.Sato, H.Kai.
  • Journal Title: Biochem Biophys Res Commun 398 Pages: 647-652
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress increases the expression and function of toll-like receptor-2 in epithelial cells. (2010)
  • Author(s): Shimasaki, S., T.Koga, T.Shuto, M.A.Suico, T.Sato, K.Watanabe, S.Morino-Koga, M.Taura, S.Okada, K.Mori, H.Kai.
  • Journal Title: Biochem Biophys Res Commun 402 Pages: 235-240
  • Peer Reviewed
• [Journal Article] CFTR-deficiency renders mice highly susceptible to cutaneous symptoms during mite infestation. (2010)
  • Author(s): Hashimoto Y, et al.
  • Journal Title: Lab Invest. Volume: 91(4) Pages: 509-518
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress increases the expression and function of toll-like receptor-2 in epithelial cells. (2010)
  • Author(s): Shimasaki S, et al.
  • Journal Title: Biochem Biophys Res Commun. Volume: 402(2) Pages: 235-240
  • Peer Reviewed
• [Journal Article] Curcumin decreases toll-like receptor-2 gene expression and function in human monocytes and neutrophils. (2010)
  • Author(s): Shuto T, et al.
  • Journal Title: Biochem Biophys Res Commun. Volume: 398(4) Pages: 647-652
  • Peer Reviewed
• [Journal Article] TLR3 induction by anticancer drugs potentiates poly I : C-induced tumor cell apoptosis. (2010)
  • Author(s): Taura M, et al.
  • Journal Title: Cancer Sci. (in press)
  • Peer Reviewed
• [Journal Article] The Endoplasmic Reticulum-associated Degradation of Transthyretin Variants Is Negatively Regulated by BiP in Mammalian Cells. (2009)
  • Author(s): Susuki S, et al.
  • Journal Title: J Biol Chem. 284(13) Pages: 8312-8321
  • Peer Reviewed
• [Journal Article] Modified Mild Heat Shock Modality Attenuates Hepatic Ischemia/Reperfusion Injury. (2009)
  • Author(s): Oba M, et al.
  • Journal Title: J Surg Res. (May 8.[Epub ahead of print]) Pages: 1-8
  • Peer Reviewed
• [Journal Article] Calreticulin positively regulates the expression and function of epithelial sodium channel. (2009)
  • Author(s): Sugahara T, et al.
  • Journal Title: Exp Cell Res. 315(19) Pages: 3294-3300
  • Peer Reviewed
• [Journal Article] Role of the glutamic acid 54 residue in transthyretin stability and thyroxine binding. (2009)
  • Author(s): Miyata M, et al.
  • Journal Title: Biochemistry 49(19) Pages: 114-123
  • Peer Reviewed
• [Journal Article] A novel combination of mild electrical stimulation and hyperthermia : general concepts and applications. (2009)
  • Author(s): Kai H, et al
  • Journal Title: Int J Hyperthermia. 25(8) Pages: 655-660
  • Peer Reviewed
• [Presentation] 糖鎖型および脱糖鎖型BCRPタンパク質のDerlin-1による負の翻訳後発現調節 (2011)
  • Author(s): 首藤剛, 杉山崇, 鈴木伸悟, 佐藤卓史, 古賀友紹, Mary Ann SUICO, 楠原洋之, 杉山雄一, 甲斐広文
  • Organizer: 第131回薬学会年会
  • Place of Presentation: 静岡(静岡県立大学)
• [Presentation] 粘液貯留を呈する新規の閉塞性肺疾患モデルマウス (2011)
  • Author(s): 首藤剛
  • Organizer: 第84回薬理学会年会
  • Place of Presentation: 横浜(パシフィコ横浜)
• [Presentation] 粘液貯留を呈する新規の閉塞性肺疾患モデルマウス (2011)
  • Author(s): 首藤剛, 甲斐広文
  • Organizer: 第84回薬理学会年会
  • Place of Presentation: パシフィコ横浜(招待講演)
• [Presentation] 糖鎖型および脱糖鎖型BCRPタンパク質のDerlin-1による負の翻訳後発現調節 (2011)
  • Author(s): 首藤剛, 杉山崇, 鈴木伸悟, 佐藤卓史, 古賀友紹, Mary Ann SUICO, 楠原洋之, 杉山雄一, 甲斐広文
  • Organizer: 第131回薬学会年会
  • Place of Presentation: 静岡県コンベンションアーツセンターツインメッセ静岡
• [Presentation] 上皮細胞における小胞体ストレス誘導時のToll様受容体2発現制御機構の解明 (2010)
  • Author(s): 島崎省吾、古賀友昭、首藤剛、Mary Ann Suico、佐藤卓史、渡邉健司、森野沙緒里、田浦学、岡田誠治、森和俊、甲斐広文
  • Organizer: 薬理学会西南部会
  • Place of Presentation: 鹿児島(かごしま県民交流センター)
  • Year and Date: 2010-11-26
• [Presentation] Mucous obstruction and impaired pulmonary mechanics in airway-specific β -epithelial Na+ channel transgenic mice (2010)
  • Author(s): Shuto T, Sugahara T, Mizuno A, Ono T, Matsumoto C, Sakaguchi Y, Koga T, Sato T, Suico MA, Koga-Morino S, Kai H
  • Organizer: 薬理学会西南部会
  • Place of Presentation: 鹿児島(かごしま県民交流センター)
  • Year and Date: 2010-11-26
• [Presentation] 難治性呼吸器疾患の病態形成とCFTR・ENaCの発現・機能異常 (2010)
  • Author(s): 首藤剛
  • Organizer: 第4回トランスポーター研究会九州部会
  • Place of Presentation: ハウステンボスユトレヒト会議室(長崎)(招待講演)
  • Year and Date: 2010-09-11
• [Presentation] 疾患関連ABCトランスポーターの発現・機能制御に基づく新たな創薬研究 (2010)
  • Author(s): 首藤剛
  • Organizer: 第25回薬物動態学会
  • Place of Presentation: 埼玉(大宮ソニックシティ)
• [Presentation] 疾患関連ABCトランスポーターの発現・機能制御に基づく新たな創薬研究 (2010)
  • Author(s): 首藤剛
  • Organizer: 第25回薬物動態学会年会
  • Place of Presentation: 大宮ソニックシティ(埼玉)(招待講演)
• [Presentation] CurcuminによるTLR2発現・機能制御 (2010)
  • Author(s): 首藤剛
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山県岡山市,岡山コンベンションセンター
• [Presentation] ABCトランスポーター分子複合体の機能・局在調節とその破綻による病態発症機構 (2009)
  • Author(s): 首藤剛
  • Organizer: 科研費特定領域研究「生体膜トランスポートソームの分子構築と生理機能」第1回班会議
  • Place of Presentation: 熊本県阿蘇市,阿蘇リゾートグランヴィリオホテル
  • Year and Date: 2009-08-27
• [Presentation] Interleukin-17A synergistically increases toll-like receptor2/4-dependent IL-8 expression in human cystic fibrosis bronchial epithelial cells (2009)
  • Author(s): Shuto T
  • Organizer: Cellular and Cytokine Interactions in Health and Disease
  • Place of Presentation: Lisbon Congress Centre, Lisbon, Portugal
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