Pathologic Analysis of Intractable Chronic Rhinosinusitis Based on Epigenetic Mechanisms

• Project/Area Number: 24592582
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Toho University
• Principal Investigator: YOSHIKAWA Mamoru 東邦大学, 医学部, 教授 (50277092)
• Research Collaborator: MATSUMOTO Kenji 国立成育医療研究センター, 免疫アレルギー・感染研究部, 部長 (60181765)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 慢性副鼻腔炎 / 気管支喘息 / ウイルス感染 / 線維芽細胞 / エピゲノム制御機構 / IFN誘導性遺伝子 / periostin / インターフェロン誘導性遺伝子

Outline of Final Research Achievements

Chronic rhinosinusitis (CRS) is characterized by local inflammation of the sinonasal tissues. CRS patients with nasal polyps and asthma often develop acute exacerbation of sinonasal symptoms after upper respiratory tract infections. Nasal fibroblasts isolated from the specimens were stimulated with poly I:C. CXCL10 expression was analyzed. Biopsy specimens were subjected to immunohistochemistry for detection of T-bet and GATA-3 expression in CD3+ T cells by double labeling. Nasal fibroblasts from the aspirin-tolerant asthma (ATA) and aspirin-intolerant asthma (AIA) patients showed significantly enhanced expression of CXCL10 mRNA and protein after poly I:C stimulation. In addition to T helper (Th)2 cells, there was more abundant infiltration of Th1 cells into tissues from the AIA and ATA patients. Our findings suggest that CRS associated with asthma may become intractable through the over-production of CXCL10 in response to viral infection.

Research Products

• [Journal Article] The usefulness of measuring tear periostin for the diagnosis and management of ocular allergic diseases. (2016)
  • Author(s): Fujishima H, Okada N, Matsumoto K, Fukagawa K, Igarashi A, Matsuda A, Ono J, Ohta S, Mukai H, Yoshikawa M, Izuhara K.
  • Journal Title: J Allergy Clin Immunol Volume: Epub ahead of print Issue: 2 Pages: 0-0
  • DOI: 10.1016/j.jaci.2015.11.039
  • NAID: 40020962730
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 好酸球性副鼻腔炎 診断ガイドライン(JESREC Study) (2015)
  • Author(s): 藤枝 重治, 坂下 雅文, 徳永 貴広, 岡野 光博, 春名 威範, 吉川 衛, 他
  • Journal Title: 日本耳鼻咽喉科学会会報 Volume: 118 Pages: 728-735
  • NAID: 130005088297
  • Open Access
• [Journal Article] 副鼻腔真菌症の診断と治療 (2015)
  • Author(s): 吉川 衛
  • Journal Title: 日本耳鼻咽喉科学会会報 Volume: 118 Pages: 629-635
  • NAID: 130005076010
  • Open Access
• [Journal Article] 好酸球性副鼻腔炎(JESREC Study) (2015)
  • Author(s): 藤枝 重治, 坂下 雅文, 徳永 貴広, 岡野 光博, 春名 威範, 吉川 衛, 他
  • Journal Title: アレルギー Volume: 64 Pages: 38-45
  • NAID: 110009908912
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 閉塞性睡眠時無呼吸に対する鼻手術の効果について Cyclic Alternating Patternを用いた検討 (2015)
  • Author(s): 森脇 宏人, 和田 弘太, 千葉 伸太郎, 恩田 信人, 澤井 理華, 吉越 彬, 渡邊 統星, 安藤 裕史, 内田 亮, 八木 朝子, 吉川 衛
  • Journal Title: 耳鼻咽喉科展望 Volume: 58 Pages: 24-30
  • NAID: 130005125832
  • Peer Reviewed
• [Journal Article] Novel scoring system and algorithm for classifying chronic rhinosinusitis: The JESREC Study. (2015)
  • Author(s): Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Yamada K, Okano M, Ohtori N, Yoshikawa M, et al
  • Journal Title: Allergy Volume: Epub ahead of print Issue: 8 Pages: 995-1003
  • DOI: 10.1111/all.12644
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased CXCL10 Expression in Nasal Fibroblasts from Patients with Refractory Chronic Rhinosinusitis and Asthma (2013)
  • Author(s): Yoshikawa M, Wada K, Yoshimura T, Asaka D, Okada N, Matsumoto K, Moriyama H.
  • Journal Title: Allergology International Volume: 62 Issue: 4 Pages: 495-502
  • DOI: 10.2332/allergolint.13-OA-0572
  • NAID: 130004873091
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin. (2013)
  • Author(s): Yoshikawa M, Kojima H, Yaguchi Y, Okada N, Saito H, Moriyama H.
  • Journal Title: PLoS One. Volume: 8(6) Issue: 6 Pages: e66725-e66725
  • DOI: 10.1371/journal.pone.0066725
  • Peer Reviewed
• [Presentation] Distinct and common gene expression profiles of nasal polyp tissues in eosinophilic and non-eosinophilic chronic rhinosinusitis. (2016)
  • Author(s): Okada N, Nakayama T, Asaka D, Matsuda A, Saito H, Yoshikawa M, Matsumoto K
  • Organizer: American Academy of Allergy, Asthma & Immunolog Annual Meeting 2016
  • Place of Presentation: Los Angels, USA
  • Year and Date: 2016-03-06
  • Int'l Joint Research
• [Presentation] 日米の鼻茸を伴う慢性副鼻腔炎における組織中遺伝子発現についての検討 (2015)
  • Author(s): 吉川 衛、浅香大也、中山次久、鴻 信義
  • Organizer: 第54回日本鼻科学会総会・学術講演会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2015-10-03
• [Presentation] 難治性の慢性副鼻腔炎に対する内視鏡下鼻内副鼻腔手術の予後についての検討 (2015)
  • Author(s): 井上なつき、中山朱里、中野光花、坂口雄介、高畑喜臣、山口宗太、大久保はるか、 森脇宏人、吉川 衛
  • Organizer: 第54回日本鼻科学会総会・学術講演会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2015-10-03
• [Presentation] Increased Th1 cells infiltration in nasal polyps from patients with refractory chronic rhinosinusitis and asthma (2015)
  • Author(s): Yoshikawa M, Wada K, Yoshimura T, Asaka D, Moriyama H
  • Organizer: EAACI Congress 2015
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-06-09
• [Presentation] 慢性副鼻腔炎の難治化因子の解明にむけて (2015)
  • Author(s): 吉川 衛
  • Organizer: 第8回埼玉上気道疾患研究会
  • Place of Presentation: パレスホテル大宮（埼玉県さいたま市）
  • Year and Date: 2015-01-22
  • Invited
• [Presentation] 好酸球性副鼻腔炎の診断基準の作成と病態解明に向けて (2014)
  • Author(s): 吉川 衛
  • Organizer: 第65回関東耳鼻咽喉科アレルギー懇話会
  • Place of Presentation: 教育会館（東京都千代田区）
  • Year and Date: 2014-09-21
  • Invited
• [Presentation] 副鼻腔真菌症の診断と治療 (2014)
  • Author(s): 吉川 衛
  • Organizer: 第115回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: ヒルトン福岡シーホーク（福岡県福岡市）
  • Year and Date: 2014-05-15
  • Invited
• [Presentation] Increased CXCL10 expression in nasal fibroblasts from patients with refractory chronic rhinosinusitis and asthma.
  • Author(s): Yoshikawa M, Wada K, Yoshimura T, Asaka D, Moriyama H
  • Organizer: European Academy of Allergy and Clinical Immunology & World Allergy Organization World Allergy & Asthma Congress 2013
  • Place of Presentation: Milan, Italy
• [Presentation] CXCL10 expression in nasal fibroblasts derived from patients with chronic rhinosinusitis
  • Author(s): Mamoru Yoshikawa, Tsuyoshi Yoshimura, Daiya Asaka, Hiroshi Moriyama
  • Organizer: 31th ISIAN & 24th ERS
  • Place of Presentation: Toulouse, France
• [Presentation] 喘息を合併した慢性副鼻腔炎患者由来の線維芽細胞におけるIP-10/CXCL10の発現について
  • Author(s): 吉川 衛、和田弘太、浅香大也、吉村 剛、森山 寛
  • Organizer: 第62回 日本アレルギー学会 秋季学術大会
  • Place of Presentation: 大阪国際会議場 (大阪府)
• [Book] アレルギー・免疫 特集 好酸球性副鼻腔炎と周辺疾患 (2015)
  • Author(s): 吉川 衛
  • Total Pages: 194
  • Publisher: 医薬ジャーナル社
• [Book] アレルギーと臨床 特集 花粉症治療の最新情報 (2015)
  • Author(s): 吉川 衛
  • Total Pages: 99
  • Publisher: 北隆館