Mechanisms of mucus overproduction and airway inflammation in asthma

• Project/Area Number: 23790905
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: FUJISAWA Tomoyuki 浜松医科大学, 医学部, 助教 (20402357)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 気道炎症 / IL-17C / 気管支喘息 / Toll-like receptor / 粘液過剰産生 / MUC5AC / MUC5B / 気道生体防御 / 気道上皮細胞 / PolyI:C / 上皮産生性サイトカイン / 抗菌ペプチド

Research Abstract

The present study was conducted to elucidate the mechanisms of mucus overproduction and airway inflammation in exacerbation of asthma.
Co-treatment with NF-kappa B activators and STAT6 activators did not show synergistic mucin genes expression in normal human bronchial epithelial (NHBE) cells. We demonstrated that polyI:C, the ligand to Toll-like receptor 3, induced IL-17C expression via TRIF/NF kappa B pathway in NHBE cells. Both IL-17C and polyI:C increased the expression of antimicrobial peptides and proinflammatory cytokines, such as human beta-defensin (hBD) 2, colony-stimulating factor (CSF) 3, and S100A12 in NHBE cells. Knockdown of IL-17 receptor E, the specific receptor for IL-17C, attenuated polyI:C-induced hBD2, CSF3, and S100A12 expression, without any reduction of polyI:C-induced IL-17C expression, which suggest that IL-17C is an essential epithelial cell-derived cytokine that enhances airway inflammation in a unique autocrine/paracrine manner in the airway epithelium.

Research Products

• [Journal Article] TLR-Mediated Airway IL-17C Enhances Epithelial Host Defense in an Autocrine/Paracrine Manner. (2014)
  • Author(s): Kusagaya H, Fujisawa T*, Yamanaka K, Mori K, Hashimoto D, Enomoto N, Inui N, Nakamura Y, Wu R, Maekawa M, Suda T, Chida K.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 50 Issue: 1 Pages: 30-39
  • DOI: 10.1165/rcmb.2013-0130oc
  • Peer Reviewed
• [Journal Article] Switching from salmeterol/fluticasone to formoterol/budesonide combinations improves peripheral airway/alveolar inflammation in asthma. (2014)
  • Author(s): Akamatsu T, Shirai T*, Kato M, Yasui H, Hashimoto D, Fujisawa T, Tsuchiya T, Inui N, Suda T, Chida K.
  • Journal Title: Pulm Pharmacol Ther. Volume: 27 Issue: 1 Pages: 52-56
  • DOI: 10.1016/j.pupt.2013.04.001
  • Peer Reviewed
• [Journal Article] Hermansky-Pudlak syndrome with nonspecific interstitial pneumonia. (2014)
  • Author(s): Furuhashi K, Enomoto N, Fujisawa T, Hashimoto D, Inui N, Nakamura Y, Suda T.
  • Journal Title: Intern Med. Volume: 53 Pages: 449-453
  • Peer Reviewed
• [Journal Article] Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study. (2013)
  • Author(s): Hozumi H, Nakamura Y, Johkoh T, Sumikawa H, Colby TV, Kono M, Hashimoto D, Enomoto N, Fujisawa T, Inui N, Suda T, Chida K.
  • Journal Title: BMJ Open. Volume: 3 Issue: 9 Pages: e003132-e003132
  • DOI: 10.1136/bmjopen-2013-003132
  • Peer Reviewed
• [Journal Article] Amount of elastic fibers predicts prognosis of idiopathic pulmonary fibrosis. (2013)
  • Author(s): Enomoto N, Suda T, Kono M, Kaida Y, Hashimoto D, Fujisawa T, Inui N, Nakamura Y, Imokawa S, Funai K, Chida K.
  • Journal Title: Respir Med. Volume: 107 Issue: 10 Pages: 1608-1616
  • DOI: 10.1016/j.rmed.2013.08.008
  • Peer Reviewed
• [Journal Article] Alveolar nitric oxide concentration reflects peripheral airway obstruction in stable asthma. (2013)
  • Author(s): Fujisawa T, Yasui H, Akamatsu T, Hashimoto D, Enomoto N, Inui N, Nakamura Y, Maekawa M, Suda T, Chida K.
  • Journal Title: Respirology Volume: 18 Issue: 3 Pages: 522-7
  • DOI: 10.1111/resp.12031
  • Peer Reviewed
• [Journal Article] Idiopathic pleuroparenchymal fibroelastosis: consideration of a clinicopathological entity in a series of Japanese patients. (2012)
  • Author(s): Kusagaya H, Nakamura Y, Kono M, Kaida Y, Kuroishi S, Enomoto N, Fujisawa T, Koshimizu N, Yokomura K, Inui N, Suda T, Colby TV, Chida K
  • Journal Title: BMC Pulm Med Volume: 72 Issue: 1 Pages: 1-7
  • DOI: 10.1186/1471-2466-12-72
  • Peer Reviewed
• [Journal Article] Rheumatoid lung disease: Prognostic analysis of 54 biopsy-proven cases． (2012)
  • Author(s): Nakamura Y
  • Journal Title: Respir Med Volume: 106(8) Issue: 8 Pages: 1164-1169
  • DOI: 10.1016/j.rmed.2012.04.004
  • Peer Reviewed
• [Journal Article] Mouse CD11bhigh lung dendritic cells have more potent capability to induce IgA than CD103+ lung dendritic cells in vitro． (2012)
  • Author(s): Suzuki Y
  • Journal Title: Am J Respir Cell Mol Biol Volume: 46(6) Issue: 6 Pages: 773-780
  • DOI: 10.1165/rcmb.2011-0329oc
  • Peer Reviewed
• [Journal Article] Impact of add-on pranlukast in stable asthma; the additive effect on peripheral airway inflammation． (2012)
  • Author(s): Yasui H
  • Journal Title: Respir Med Volume: 106(4) Issue: 4 Pages: 508-514
  • DOI: 10.1016/j.rmed.2011.12.014
  • Peer Reviewed
• [Journal Article] Ulcerating bronchitis caused by cytomegalovirus in a patient with polymyositis. (2012)
  • Author(s): Hozumi H, Fujisawa T, Kuroishi S, Inui N, Nakamura Y, Suda T, Chida K.
  • Journal Title: Intern Med. Volume: 51 Pages: 2933-6
  • Peer Reviewed
• [Journal Article] Impact of add-on pranlukast in stable asthma; the additive effect on peripheral airway inflammation (2012)
  • Author(s): Yasui H, Fujisawa T, Inui N, Kato M, Hashimoto D, Enomoto N, Nakamura Y, Shirai T, Suda T, Nakamura H, Chida K
  • Journal Title: Respir Med Volume: 106 Pages: 508-514
  • Peer Reviewed
• [Journal Article] Mouse Lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T cell responses (2012)
  • Author(s): Furuhashi K, Suda T, Hasegawa H, Suzuki Y, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Shibata K, Nakamura H, Chida K
  • Journal Title: Am J Respir Cell Mol Biol Volume: 46 Pages: 165-172
  • Peer Reviewed
• [Journal Article] 外来市中肺炎治療における炎症性マーカーについて (2012)
  • Author(s): 古橋一樹，藤澤朋幸，早川啓史，横村光司，豊嶋幹生，安田和雅，菅沼秀基，白井敏博，山田孝，増田昌文，千田金吾
  • Journal Title: 日本呼吸器学会雑誌 Volume: 5
  • NAID: 10030633549
  • Peer Reviewed
• [Journal Article] Serum activity of indoleamine 2,3-dioxygenase predicts prognosis of community-acquired pneumonia (2011)
  • Author(s): Suzuki Y, Suda T, Yokomura K, Suzuki M, Fujie M, Furuhashi K, Hahimoto D, Enomto N, Fujisawa T, Nakamura Y, Inui N, Nakano Y, Nakamura H, Chida K
  • Journal Title: J Infect Volume: 63 Pages: 215-222
  • Peer Reviewed
• [Journal Article] 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced MUC5AC expression: aryl hydrocarbon receptor-independent/EGFR/ERK/p38-dependent SP1-based transcription. (2011)
  • Author(s): Lee YC, Oslund KL, Thai P,Velichko S, Fujisawa T, Duong T, Denison MS, Wu R
  • Journal Title: Am J Respir Cell Mol Biol Volume: 45 Pages: 270-276
  • Peer Reviewed
• [Journal Article] NF-κB mediates IL-1β- and IL-17A-induced MUC5B expression in airway epithelial cells (2011)
  • Author(s): Fujisawa T, Chang MM, Velichko S, Thai P, Hung LY, Huang F, Phuong N, Chen Y, Wu R
  • Journal Title: Am J Respir Cell Mol Biol Volume: 45 Pages: 246-252
  • Peer Reviewed
• [Presentation] Profile of IL-17C expression in human bronchial epithelial cells (2014)
  • Author(s): Kusagaya H, Fujisawa T, et al.
  • Organizer: American Thoracic Society 2014
  • Place of Presentation: サンディエゴ、アメリカ合衆国
• [Presentation] 気道上皮細胞においてTLRを介して誘導されたIL-17Cは自己分泌的に気道生体防御を増強する (2014)
  • Author(s): 草ケ谷秀樹、藤澤朋幸, 他
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪
• [Presentation] ヒト気道上皮細胞におけるTLRを介したIL-17Cの制御機構と機能についての検討 (2013)
  • Author(s): 草ケ谷秀樹、藤澤朋幸, 他
  • Organizer: 第63回日本アレルギー学会秋期学術大会
  • Place of Presentation: 東京
• [Presentation] Alveolar Nitric Oxide Concentration Reflects Peripheral Airway Obstruction In Stable Asthma (2013)
  • Author(s): Fujisawa T, et al.
  • Organizer: American Thoracic Society 2013
  • Place of Presentation: フィラデルフィア、アメリカ合衆国
• [Presentation] Alveolar Nitric Oxide Concentration Reflects Peripheral Airway Obstruction In Stable Asthma. (2013)
  • Author(s): Fujisawa T, Yasui H, Aakamatsu T, Hashimoto D, Enomoto N, Inui N, Nakamura Y, Maekawa M, Suda T, Chida K
  • Organizer: American Thoracic Society
  • Place of Presentation: Philadelphia
• [Presentation] ヒト気道上皮細胞におけるTLRを介したIL-17Cの制御機構と機能についての検討． (2013)
  • Author(s): 草ヶ谷英樹，藤澤朋幸，森和貴，山中勝正，橋本大，榎本紀之，中村祐太郎，乾直輝，須田隆文
  • Organizer: 第63回日本アレルギー学会秋期学術大会．
  • Place of Presentation: 東京
• [Presentation] 関節リウマチおよびシェーグレン症候群の治療中に，両肺野にすりガラス陰影と班状影を呈した1例 (2013)
  • Author(s): 藤澤朋幸，榎本紀之，長谷川浩嗣，中村祐太郎，河野雅人，橋本大，乾直輝，須田隆文，千田金吾
  • Organizer: 第53回日本呼吸器学会総会
  • Place of Presentation: 東京
• [Presentation] 当院におけるICTラウンドの現状と課題 (2013)
  • Author(s): 藤澤朋幸，澤木ゆかり，名倉理教，八木達也，山田尚広，菊池直香，橋本大，前川真人
  • Organizer: 第28回日本環境感染学会総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 気管支喘息患者におけるAlveolar NO濃度に関わる因子の検討 (2012)
  • Author(s): 藤澤朋幸, 他
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
• [Presentation] 気管支喘息患者における補正肺胞由来NO濃度の解析 (2012)
  • Author(s): 藤澤朋幸，飯野和美，橋本大，須田隆文，千田金吾，前川真人
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 京都
• [Presentation] 透析室改修工事に際した環境感染対策 (2012)
  • Author(s): 藤澤朋幸, 澤木ゆかり, 名倉理教, 橋本大, 八木達也, 山田尚弘, 加藤明彦, 前川真人
  • Organizer: 第27回 日本環境感染学会総会
  • Place of Presentation: 博多
• [Presentation] 気管支喘息患者におけるalveolar NO濃度に関わる因子の検討 (2011)
  • Author(s): 藤澤朋幸，橋本大，飯野和美，千田金吾，竹下明裕，前川真人
  • Organizer: 第58回日本臨床検査医学会学術集会
  • Place of Presentation: 岡山
• [Book] I型アレルギーのバイオマーカー.臨床検査. Vol58, No.2 (2014)
  • Author(s): 藤澤朋幸
  • Publisher: 医学書院
• [Book] 臨床検査 Vol58, No.2 I型アレルギーのバイオマーカー (2014)
  • Author(s): 藤澤朋幸
  • Total Pages: 284
  • Publisher: 医学書院
• [Book] Q & Aでわかる呼吸器疾患ガイドライン実践ブック (2013)
  • Author(s): 藤澤朋幸，千田金吾，須田隆文，乾直輝，中村祐太郎
  • Total Pages: 221
  • Publisher: 南江堂
• [Book] 病態生理.新しい診断と治療のABCサルコイド-シス (2012)
  • Author(s): 藤澤朋幸,千田金吾
  • Publisher: 最新医学社
• [Book] 病態生理．新しい診断と治療のABCサルコイド－シス (2012)
  • Author(s): 藤澤朋幸，千田金吾
  • Total Pages: 8
  • Publisher: 最新医学社
• [Book] 膠原病に合併する間質性肺炎.特発性間質性肺炎-最近の進歩と展望- (2011)
  • Author(s): 藤澤朋幸,榎本紀之、千田金吾
  • Publisher: 最新医学社
• [Book] 必携 内科検査・手技マニュアル ―この一冊ですべてがわかる- (2011)
  • Author(s): 藤澤朋幸、林秀晴、千田金吾
  • Total Pages: 393
  • Publisher: 南江堂
• [Book] 膠原病に合併する間質性肺炎． 特発性間質性肺炎 -最近の進歩と展望- (2011)
  • Author(s): 藤澤朋幸，榎本紀之､千田金吾
  • Total Pages: 156
  • Publisher: 最新医学社