Therapeutic approach using analysis of type III IFN SNPs in upper respiratory disease

• Project/Area Number: 24659750
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: Sapporo Medical University
• Principal Investigator: HIMI Tetsuo 札幌医科大学, 医学部, 教授 (90181114)
• Co-Investigator(Renkei-kenkyūsha): KOJIMA Takashi 札幌医科大学, 医学部, 教授 (30260764) ; TSUTSUMI Hiroyuki 札幌医科大学, 医学部, 教授 (80217348)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インターフェロン / 遺伝子多型 / 鼻粘膜 / 上皮細胞 / ウイルス受容体 / ＲＳＶ / 自然免疫 / プロテアーゼ / クルクミン / タイト結合 / RSウイルス / ウイルス複製

Research Abstract

Respiratory syncytial virus (RSV) is the major cause of respiratory disease. The human nasal epithelium is the first line of defense during respiratory virus infection. RSV could infect these cells from apical but not basolateral side, and enhanced the expression of tight junction proteins. RSV infection induces polarity in the infected cells, thereby spreading the infection.
As an innate immune response against diverse viral infections, a host induces two types of IFN, type-I and type-III. Type -III, but not type-I, contributes to the main first line defense against respiratory virus infection in nasal mucosa. Curcumin and Humulon can prevent the replication of RSV and the epithelial responses to it. Moreover, Clarithromycin also suppressed RSV-induced PAF receptor expression and adhesion of fluorescein-labeled S. pneumoniae cells to A549 cells. These are useful biological products for the prevention and therapy for RSV infection.

Research Products

• [Journal Article] Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells (2014)
  • Author(s): Nomura K, Takano K, Himi T, Kojima T. (10名, 9, 10番)
  • Journal Title: Respir Res Volume: 18 Issue: 1 Pages: 15-21
  • DOI: 10.1186/1465-9921-15-21
  • Peer Reviewed / Open Access
• [Journal Article] The clinical characteristics of patients with IgG4-related disease with infiltration of the labial salivary gland by IgG4-positive cells (2014)
  • Author(s): Abe A, Takano K, Seki N, Himi T. (7名7番)
  • Journal Title: Mod Rheumatol Volume: 26 Issue: 6 Pages: 949-952
  • DOI: 10.3109/14397595.2014.891964
  • URL: http://informahealthcare.com/doi/abs/
  • Peer Reviewed
• [Journal Article] The role of cytotoxic T cells in IgG4-related dacryoadenitis and sialadenitis, the so-called Mikulic's disease (2014)
  • Author(s): T abeya T, Seki N, Takano K, Himi T
  • Journal Title: Mod Rheumatol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Curcumin prevents replication of RS virus and the epithelial responses to it in human nasal epithelial cells (2013)
  • Author(s): Obata K, Kojima T, Yokota S, Tsutsumi H, Himi T. (全15名2, 14番)
  • Journal Title: PLoS One Volume: 8(9) Issue: 9 Pages: 70225-70225
  • DOI: 10.1371/journal.pone.0070225
  • Peer Reviewed
• [Journal Article] Marked induction of MMP-10 by RS virus infection in human nasal epithelial cells (2013)
  • Author(s): Hirakawa S, Kojima T, Yokota SI, Himi T,, (全15名5, 9番)
  • Journal Title: J Med Virol Volume: 85(12) Issue: 12 Pages: 2141-50
  • DOI: 10.1002/jmv.23718
  • Peer Reviewed
• [Journal Article] Expression and localization of purinergic P2Y(12) receptor in human nasal mucosa (2013)
  • Author(s): Shirasaki H, Himi T(全4名)
  • Journal Title: Allergol Int Volume: 62(2) Pages: 239-44
  • NAID: 130004873071
  • Peer Reviewed
• [Journal Article] Localization and Up-Regulation of Cysteinyl Leukotriene-2 Receptor in Human Allergic Nasal Mucosa (2013)
  • Author(s): Shirasaki H, Himi T(全6名6番)
  • Journal Title: Allergology International Volume: 62 Issue: 2 Pages: 223-228
  • DOI: 10.2332/allergolint.12-OA-0490
  • NAID: 130004873068
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Regulation of tight junctions in upper airway epithelium (2013)
  • Author(s): Kojima T, Takano K, Himi T(全19名1, 3, 18番)
  • Journal Title: Biomed Res Int Volume: 2013 Pages: 947072-947072
  • DOI: 10.1155/2013/947072
  • Peer Reviewed
• [Journal Article] Humulone suppresses replication of RS virus and release of IL-8 and RANTES in normal human nasal epithelial cells (2013)
  • Author(s): Fuchimoto J, Kojima T, Yokota SI, Himi T(全15名2. 14番)
  • Journal Title: Med Mol Morphol Volume: 46(4) Issue: 4 Pages: 203-9
  • DOI: 10.1007/s00795-013-0024-1
  • Peer Reviewed
• [Journal Article] Necessity of early intervention for IgG4-related disease--delayed treatment induces fibrosis progression (2013)
  • Author(s): Shimizu Y, Himi T(全20名15番)
  • Journal Title: Rheumatology (Oxford) Volume: 52(4) Issue: 4 Pages: 679-83
  • DOI: 10.1093/rheumatology/kes358
  • Peer Reviewed
• [Journal Article] 総論「上気道と上部消化管のアレルギー」 (2013)
  • Author(s): 氷見徹夫
  • Journal Title: アレルギーの臨床 Volume: 33(8) Pages: 806-806
• [Journal Article] ウイルス性上気道炎での免疫応答と鼻粘膜上皮の役割 (2013)
  • Author(s): 氷見徹夫,高野賢一,大國毅,小笠原徳子,正木智之,小幡和史,堤裕幸,小島隆,澤田典均,横田伸一
  • Journal Title: 耳鼻咽喉科展望 Volume: 56 Pages: 162-77
  • NAID: 130004679511
• [Journal Article] Expression and Localization of Purinergic P2Y₁₂ Receptor in Human Nasal Mucosa (2013)
  • Author(s): Shirasaki H, Kanaizumi E, Seki N, Kikuchi M, Himi T.
  • Journal Title: Allergology International Volume: 62 Issue: 2 Pages: 239-244
  • DOI: 10.2332/allergolint.12-OA-0496
  • NAID: 130004873071
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Humulone suppresses replication of respiratory syncytial virus and release of IL-8 and RANTES in normal human nasal epithelial cells. (2013)
  • Author(s): Fuchimoto J
  • Journal Title: Med Mol Morphol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Hop water extract inhibits double-stranded RNA-induced thymic stromal lymphopoietin release from human nasal epithelial cells (2012)
  • Author(s): Fuchimoto J, Kojima T, Himi T(全12名2, 11番)
  • Journal Title: Am J Rhinol Allergy Volume: 26(6) Issue: 6 Pages: 433-8
  • DOI: 10.2500/ajra.2012.26.3814
  • Peer Reviewed
• [Journal Article] Localization and upregulation of the nasal histamine H1 receptor in perennial allergic rhinitis (2012)
  • Author(s): Shirasaki H, Himi T(全4名34番)
  • Journal Title: Mediators Inflamm Volume: 2012 Pages: 951316-951316
  • DOI: 10.1155/2012/951316
  • Peer Reviewed
• [Journal Article] Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy (2012)
  • Author(s): Hayashi J, Himi T(全11名)
  • Journal Title: Oncol Lett Volume: 4(1) Pages: 151-155
  • Peer Reviewed
• [Journal Article] Clarithromycin suppresses human respiratory syncytial virus infection-induced Streptococcus pneumoniae adhesion and cytokine production in a pulmonary epithelial cell line (2012)
  • Author(s): Yokota S, Himi T(全6名5番)
  • Journal Title: Mediators Inflamm Volume: 2012 Pages: 528568-528568
  • DOI: 10.1155/2012/528568
  • Peer Reviewed
• [Journal Article] Sorting Nexin 5 of a New Diagnostic Marker of Papillary Thyroid Carcinoma Regulates Caspase-2 (2012)
  • Author(s): Ara S,Kikuchi T,Matsumiya H,Kojima T,Kubo T, Ye RC, Sato A, Kon SI, Honma T,Asakura K, Hasegawa T, Himi T,Sato N, Ichimiya S.
  • Journal Title: Cancer Science Volume: 103 Issue: 7 Pages: 1356-62
  • DOI: 10.1111/j.1349-7006.2012.02296.x
  • Peer Reviewed
• [Journal Article] A novel concept of Mikulicz's disease as IgG4-related disease (2012)
  • Author(s): Himi T, Takano K(全5名)
  • Journal Title: Auris Nasus Larynx Volume: 39(1) Pages: 9-17
  • Peer Reviewed
• [Journal Article] Malignant melanoma of the head and neck : A multi-institutional retrospective analysis of cases in Northern Japan (2012)
  • Author(s): Shiga K, Ogawa T, Kobayashi T, Ueda S, Kondo A, Nanba A, Kuwashima S, Asada Y, Suzuki S, Nagahashi T, Takahashi M, Suzuki M, Ishida A, Watanabe K, Harabuchi Y, Himi T, Shinkawa H, Sato H, Saijyo S, Fukuda S, Tanaka K, Ishikawa K, Omori K, Aoyagi M, Hashimoto S
  • Journal Title: Head Neck Volume: (in press) Issue: 11 Pages: 1537-1541
  • DOI: 10.1002/hed.21984
  • Peer Reviewed
• [Journal Article] Regulation of IL-33 and TSLP in human nasal fibroblasts by proinflammatory cytokines (2012)
  • Author(s): Nomura K, Kojima T, Himi T(全7名2. 6番)
  • Journal Title: Laryngoscope Volume: 122(6) Issue: 6 Pages: 1185-92
  • DOI: 10.1002/lary.23261
  • Peer Reviewed
• [Journal Article] The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis (2012)
  • Author(s): Kamekura R, Kojima T, Himi T(全6名2, 6番)
  • Journal Title: Clin Exp Allergy Volume: 42(2) Issue: 2 Pages: 218-28
  • DOI: 10.1111/j.1365-2222.2011.03867.x
  • Peer Reviewed
• [Journal Article] Anti-leukotriene therapy may be effective for the treatment of salivary eosinophilic inflammation (2012)
  • Author(s): Shirasaki H, Himi T ( 全3名3番)
  • Journal Title: Allergol Int Volume: 61(1) Pages: 175-6
  • DOI: 10.1155/2011/259867
  • NAID: 130004873036
  • Peer Reviewed
• [Journal Article] Risk of malignancies in IgG4-related disease (2012)
  • Author(s): Yamamoto M, Himi T(全13名11番)
  • Journal Title: Mod Rheumatol Volume: 22(3) Issue: 3 Pages: 414-8
  • DOI: 10.1007/s10165-011-0520-x
  • NAID: 10030782273
  • Peer Reviewed
• [Journal Article] Spontaneous regression of lung lesions after excision of the submandibular gland in a patient with chronic sclerosing sialadenitis (2012)
  • Author(s): Seki N, Himi T(全5名5番)
  • Journal Title: Auris Nasus Larynx Volume: 39(2) Issue: 2 Pages: 212-5
  • DOI: 10.1016/j.anl.2011.01.025
  • Peer Reviewed
• [Journal Article] Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases (2011)
  • Author(s): Yamamoto M, Tabeya T, Naishiro Y, Yajima H, Ishigami K, Shimizu Y, Obara M, Suzuki C, Yamashita K, Yamamot H, Hayashi T, Sasaki S, Suzuki Y, Nishimoto N, Honda S, Takahashi H, Imai K, Shinomura Y
  • Journal Title: Mod Rheumatol Volume: (Epub ahead of print) Issue: 3 Pages: 419-25
  • DOI: 10.1007/s10165-011-0532-6
  • NAID: 10030782295
  • Peer Reviewed
• [Presentation] ウイルス性炎症における上気道粘膜の役割 (2013)
  • Author(s): 氷見徹夫
  • Organizer: 第1回日本耳鼻咽喉科感染症・エアロゾル学会総会・学術講演会ランチョンセミナー
  • Place of Presentation: 大分市
  • Year and Date: 2013-09-06
• [Presentation] 扁桃・アデノイドはなぜあるのか?鼻はなにをしているのか?-小児の粘膜免疫・粘膜防御最前線 (2013)
  • Author(s): 氷見徹夫
  • Organizer: 第8回日本小児耳鼻咽喉科学会ミートザエキスパート
  • Place of Presentation: 前橋市
  • Year and Date: 2013-06-20
• [Presentation] 宿題報告上気道炎症における鼻粘膜の役割 (2012)
  • Author(s): 氷見徹夫
  • Organizer: 第113回日本耳鼻咽喉科学会学術講演会
  • Place of Presentation: 新潟
  • Year and Date: 2012-05-11
• [Presentation] 宿題報告 上気道炎症における鼻粘膜の役割 (2012)
  • Author(s): 氷見徹夫
  • Organizer: 第113回日本耳鼻咽喉科学会
  • Place of Presentation: 新潟
  • Invited
• [Presentation] Localization and upregulation of CysLT2 R in perennial allergic rhinitis (2012)
  • Author(s): Shirasaki H
  • Organizer: 2012 WAO
  • Place of Presentation: インド
• [Presentation] ウイルス性炎症における上気道粘膜の役割
  • Author(s): 氷見徹夫
  • Organizer: 日本耳鼻咽喉科感染症・エアロゾル学会
  • Place of Presentation: 大分
  • Invited
• [Presentation] 鼻粘膜上皮と樹状細胞の役割
  • Author(s): 高野賢一
  • Organizer: 日本アレルギー学会
  • Place of Presentation: 横浜
• [Presentation] 鼻粘膜上皮におけるＲＳウイルス感染メカニズムと新たな予防戦略
  • Author(s): 高野賢一，氷見徹夫
  • Organizer: 日本鼻科学会
  • Place of Presentation: 福井
  • Invited
• [Book] 上気道炎症における鼻粘膜の役割 (2012)
  • Author(s): 氷見徹夫
  • Publisher: アイワード
• [Book] 上気道炎症における鼻粘膜の役割 (2012)
  • Author(s): 氷見徹夫
  • Total Pages: 433
  • Publisher: アイワード札幌