Cross-talk between TNF-LIGHT and nitrosative stress in the airway remodeling of asthma

• Project/Area Number: 25461502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Yamaguchi University (2015); Wakayama Medical University (2013-2014)
• Principal Investigator: HIRANO TSUNAHIKO 山口大学, 医学部附属病院, 准教授 (00382333)
• Co-Investigator(Kenkyū-buntansha): KANAI Kuninobu 和歌山県立医科大学, 医学部, 学内助教 (90649055)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: TNF-LIGHT / 窒素化ストレス / 呼気NO / 難治性喘息 / 気道リモデリング / クロストーク / TNF-LIGTH / 呼気ＮＯ

Outline of Final Research Achievements

The molecular mechanism of airway remodeling in patients with asthma is not fully understood. TNF family member LIGHT (LIGHT) expressed on inflammatory cells may trigger airway remodeling via TGF-beta or IL13 overexpression. Moreover, patients with severe asthma are reported to have more nitrosative stress than patients with non-severe asthma.Therefore,the aim of this study is to elucidate whether there is cross-talk between LIGHT and nitrosative stress in the fixed airway obstruction of asthma.
Asthmatic patients with airway obstruction despite usual treatment and asthmatic patients with favorable pulmonary function were enrolled.Induced sputum was collected and LIGHT and 3-nitrotyrosine (3-NT), which is a footprint of nitrosative stress, were quantified by immunohistochemical staining.
As a result,it was suggested that cross-talk between LIGHT and nitrosative stress might be related to the pathophysiology of airway remodeling in asthma.

Research Products

• [Journal Article] Stratifying the risk of COPD exacerbati on using the modified Medical Research Council scale: A multicenter cross-sectional CAP study. (2015)
  • Author(s): Matsunaga, K, A. Hayata, K. Akamatsu, T. Hirano, T. Tamada, T. Kamei, T. Tsuda, H. Nakamura, T. Takahashi, S. Hozawa, Y. Mori, Y. Sakamoto, K. Kimura, U. Katsumata, M. Miura, M. Ichinose.
  • Journal Title: Respiratory Investigation Volume: 53 Issue: 2 Pages: 82-85
  • DOI: 10.1016/j.resinv.2014.10.006
  • Peer Reviewed / Open Access
• [Journal Article] Progression of Irreversible Airflow Limitation in Asthma: Correlation with Severe Exacerbations (2015)
  • Author(s): Matsunaga K, Hirano T, Oka A, Tanaka A, Kanai K, Kikuchi T, Hayata A, Akamatsu H, Akamatsu K, Koh Y, Nakanishi M, Minakata Y, Yamamoto N
  • Journal Title: J Allergy Clin Immunol Pract Volume: 3 Issue: 5 Pages: 759-764
  • DOI: 10.1016/j.jaip.2015.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Response to Systemic Corticosteroids on Persistently High Exhaled Nitric Oxide in Severe Asthma. (2015)
  • Author(s): Hirano T, Ito K, Edakuni N, Matsunaga K
  • Journal Title: J Allergy Ther Volume: 6 Issue: 04 Pages: 2-4
  • DOI: 10.4172/2155-6121.1000219
  • Peer Reviewed / Open Access
• [Journal Article] Cigarette smoke augments MUC5AC production via the TLR3-EGFR pathway in airway epithelial cells. (2015)
  • Author(s): K. Kanai, A. Koarai, Y.Shishikura, H. Sugiura, T. Ichikawa, T. Kikuchi, K. Akamatsu, T. Hirano, M. Nakanishi, K. Matsunaga, Y. Minakata and M.Ichinose.
  • Journal Title: Respir Investig. Volume: in press Issue: 4 Pages: 137-148
  • DOI: 10.1016/j.resinv.2015.01.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of pharmacologic treatment based on airflow limitation and breathlessness on daily physical activity in patients with chronic obstructive pulmonary disease (2015)
  • Author(s): Minakata Y, Morishita Y, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Ichinose M
  • Journal Title: Int J Chron Obstruct Pulmon Dis Volume: 10 Pages: 1275-1282
  • DOI: 10.2147/copd.s84134
  • Peer Reviewed / Open Access
• [Journal Article] TLR3 activation augments matrix metalloproteinase production through reactive nitrogen species generation in human lung fibroblasts. (2014)
  • Author(s): Ichikawa T, Sugiura H, Koarai A, Minakata Y, Kikuchi T, Morishita Y, Oka A, Kanai K, Kawabata H, Hiramatsu M, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Yamamoto N, Ichinose M.
  • Journal Title: J Immunol Volume: 192 Issue: 11 Pages: 4977-4988
  • DOI: 10.4049/jimmunol.1302919
  • Peer Reviewed
• [Journal Article] Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline (2014)
  • Author(s): Kazuto Matsunaga
  • Journal Title: Respiratory Medicine Volume: 108 Issue: 7 Pages: 976-982
  • DOI: 10.1016/j.rmed.2014.04.014
  • Peer Reviewed
• [Journal Article] Reduced level of physical activity in Japanese patients with chronic obstructive pulmonary disease (2014)
  • Author(s): Minakata Y, Sugino A, Kanda M, Ichikawa T, Akamatsu K, Koarai A, Hirano T, Nakanishi M, Sugiura H, Matsunaga K, Ichinose M
  • Journal Title: Respiratory investigation Volume: 52 Issue: 1 Pages: 41-48
  • DOI: 10.1016/j.resinv.2013.06.002
  • Peer Reviewed
• [Journal Article] Ongoing Allergic Rhinitis Impairs Asthma Control by Enhancing the Lower Airway Inflammation (2014)
  • Author(s): Oka A, Matsunaga K, Kamei T, Sakamoto Y, Hirano T, Hayata A, Akamatsu K, Kikuchi T, Hiramatsu M, Ichikawa T, Nakanishi M, Minakata Y, Yamamoto N
  • Journal Title: J Allergy Clin Immunol Pract Volume: 2 Issue: 2 Pages: 172-178
  • DOI: 10.1016/j.jaip.2013.09.018
  • Peer Reviewed
• [Journal Article] Difference in time-course of improvement in asthma control measures between budesonide and budesonide/formoterol (2013)
  • Author(s): Matsunaga K
  • Journal Title: Pulm Pharmacol Ther Volume: 26 Issue: 2 Pages: 189-194
  • DOI: 10.1016/j.pupt.2012.10.006
  • Peer Reviewed
• [Journal Article] Persistent elevation of exhaled nitric oxide and modification of corticosteroid therapy in asthma. (2013)
  • Author(s): T. Hirano, H. Sugiura et al.
  • Journal Title: Respir Invest Volume: 51 Issue: 2 Pages: 84-91
  • DOI: 10.1016/j.resinv.2013.01.002
  • Peer Reviewed
• [Journal Article] 25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway (2013)
  • Author(s): Tomohiro Ichikawa
  • Journal Title: Experimental Cell Research Volume: 319 Issue: 8 Pages: 1176-1186
  • DOI: 10.1016/j.yexcr.2013.02.014
  • Peer Reviewed
• [Journal Article] Predictors for Identifying the Efficacy of Systemic Steroids on Sustained Exhaled Nitric Oxide Elevation in Severe Asthma (2013)
  • Author(s): Matsunaga K, Hirano T, Akamatsu K, Minakata Y
  • Journal Title: Allergology International Volume: 62 Issue: 3 Pages: 359-365
  • DOI: 10.2332/allergolint.12-OA-0530
  • NAID: 130004477190
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Relationship between alveolar nitric oxide concentration in exhaled air and small airway function in COPD. (2013)
  • Author(s): T. Hirano, H. Sugiura et al.
  • Journal Title: J Breath Res Volume: 7 Issue: 4 Pages: 046002-046002
  • DOI: 10.1088/1752-7155/7/4/046002
  • Peer Reviewed
• [Journal Article] Effect of Transdermal Tulobuterol Patch on the Physical Activity in Eight Male Subjects with Chronic Obstructive Pulmonary Disease. (2013)
  • Author(s): Minakata Y, Morishita Y, Hiramatsu M, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K and Ichinose M
  • Journal Title: Clin Res Pulmonol Volume: 1 Pages: 1010-1010
  • Peer Reviewed
• [Presentation] 広域周波オシレーション法とFeNO測定を組み合わせた喘息の病態把握が有用であった一例. (2015)
  • Author(s): 関根敏勝, 中塚賢一, 井上良子, 小川智寿美, 瀧口良重, 大石博晃, 平野綱彦,赤水尚史:
  • Organizer: 第55回日臨技近畿支部医学検査学会
  • Place of Presentation: 大阪府大阪市（大阪国際交流センター）
  • Year and Date: 2015-10-18
• [Presentation] 高齢進行期胸部悪性腫瘍患者においてGFR値を予測する新たな推算式の検討. (2015)
  • Author(s): 菊池崇史, 赤松弘朗, 盛啓太, 金井一修, 赤松啓一郎, 洪泰浩, 中西正典, 松永和人, 上田弘樹, 山本信之
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: 北海道札幌市（ロイトン札幌）
  • Year and Date: 2015-07-16
• [Presentation] VBNとEBUS-GSによって診断し得たクリプトコッカス症の二例. (2015)
  • Author(s): 岡亜早子, 田中彩加, 金井一修, 菊池崇史, 早田敦志, 赤松弘朗, 市川朋宏, 赤松啓一郎, 洪泰浩, 中西正典, 松永和人, 平野綱彦, 中村靖司, 山本信之
  • Organizer: 第38回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 東京都新宿（京王プラザホテル）
  • Year and Date: 2015-06-12
• [Presentation] Statifying the risk of COPD exacerbation using the modified Medical Research Council scale: a multicenter cross-sectional CAP study. (2015)
  • Author(s): Matsunaga K, Oka A, Hayata A, Akamtsu K, Hirano T, Ichinose M
  • Organizer: 2015 ATS International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-19
  • Int'l Joint Research
• [Presentation] Effect of Inhaled Short-Acting Bate-2 Agonist (Procaterol) on Physical Activity of Patients with Chronic Obstructive Pulmonary disease. (2015)
  • Author(s): Hirano T, Matsunaga K, Ogawa H, Minakata Y, Akamatsu K, Nakanishi M, Ichikawa T, Ichinose M
  • Organizer: 2015 ATS International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Presentation] 当院気管支鏡検査における迅速細胞診(Rapid on-site evaluation ; ROSE)の検討. (2015)
  • Author(s): 金井一修, 赤松弘朗, 松本安子, 田中彩加, 菊池崇史, 洪泰浩, 中西正典, 松永和人, 平野綱彦, 山本信之
  • Organizer: 第112回日本内科学会講演会
  • Place of Presentation: 京都府京都市（みやこめっせ）
  • Year and Date: 2015-04-11
• [Presentation] 喘息治療の新展開 (2015)
  • Author(s): 平野 綱彦
  • Organizer: 日高医師会学術講演会
  • Place of Presentation: 御坊市
  • Year and Date: 2015-03-17
  • Invited
• [Presentation] 日常診療に潜むCOPDの診断と管理の工夫 (2014)
  • Author(s): 平野 綱彦
  • Organizer: 第266回生涯教育月例会
  • Place of Presentation: 有田市
  • Year and Date: 2014-12-10
  • Invited
• [Presentation] ぜんそく、COPDの鑑別に苦慮する症例の対応 (2014)
  • Author(s): 平野 綱彦
  • Organizer: Chest Conference in Wakayama
  • Place of Presentation: 和歌山市
  • Year and Date: 2014-11-27
  • Invited
• [Presentation] 呼吸器疾患における治療標的としてのNOの有用性. (2014)
  • Author(s): 平野 綱彦
  • Organizer: 第39回呼吸器疾患研究会
  • Place of Presentation: 和歌山市
  • Year and Date: 2014-11-20
  • Invited
• [Presentation] ASSOCIATION OF SEVERE EXACERBATION WITH FEV1 DECLINE AND LOSS OF AIRWAY REVERSIBILITY ASTHMA. (2014)
  • Author(s): Matsunaga K, Ichikawa T, Akamatsu K, Hirano T.
  • Organizer: 2014 ERS International Congress
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] PERSISTENTLY HIGH EXHALED NITRIC OXIDE AND LUNG FUNCTION DECLINE IN PATIENTS WITH CONTROLLED ASTHMA AT BASELINE. (2014)
  • Author(s): Matsunaga K, Ichikawa T, Akamatsu K, Hirano T.
  • Organizer: 2014 ERS International Congress
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] COPD患者の日常活動性の測定システム開発とその臨床応用. (2014)
  • Author(s): 平野 綱彦
  • Organizer: 54回臨床呼吸機能講習会
  • Place of Presentation: 東京
  • Year and Date: 2014-08-29
  • Invited
• [Presentation] COPD患者の身体活動性に対する短時間作用性吸入β2刺激薬・プロカテロールの効果. (2014)
  • Author(s): 平野綱彦, 松永和人, 小川浩正, 南方良章, 赤松啓一郎, 中西正典, 市川朋宏, 本多雄一, 杉野亮人, 洪泰浩, 赤松弘朗, 早田敦志, 菊池崇史, 金井一修, 岡亜早子, 田中彩加, 山本信之, 一ノ瀬正和
  • Organizer: TOKYO ASIA COPD SYMPOSIUM 2014
  • Place of Presentation: 東京
  • Year and Date: 2014-07-05
• [Presentation] Cigarette smoke augments MUC5AC mucin production via TLR3-EGFR pathway in airway epithelial cells. (2014)
  • Author(s): Kanai K, Koarai A, Sugiura H, Ichikawa T, Kikuchi T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, and Ichinose M
  • Organizer: 2014 ATS International Conference
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-05-22
• [Presentation] Changes in forced expiratiry volume in 1 second over time in patients with controlled asthma at baseline. (2014)
  • Author(s): Matsunaga K, Ichikawa T, Oka A, Morishita Y, Kanai K, Hiramatsu M, Akamatsu H, Kawabata H, Kikuchi T, Akamatsu K, Hirano T, Koh Y, Nakanishi M, Minakata Y, Yamamoto N
  • Organizer: The 54th Annual Meeting of The Japanese Respiratory Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2014-04-27
• [Presentation] COPD患者の日常活動量に対する短時間作用性吸入β2刺激薬・プロカテロールの効果の検討. (2014)
  • Author(s): 平野綱彦
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-04-25
  • Invited
• [Presentation] Predictors for identifying the efficacy of systemic steroids on sustained exhaled nitric oxide elevation in severe asthma.
  • Author(s): T. Hirano
  • Organizer: The 23rd Congress of Interasma Japan/North Asia
  • Place of Presentation: 東京
• [Presentation] Cigarette smoke augments MUC5AC mucin production via TLR3-EGFR pathway in airway epithelial cells.
  • Author(s): K. Kanai, A. Koarai, H. Sugiura, T. Ichikawa, T. Kikuchi, K. Akamatsu, T. Hirano, M. Nakanishi, K. Matsunaga, Y. Minakata and M. Ichinose.
  • Organizer: 2013 ERS Annual Congress
  • Place of Presentation: Barcelona , Spain
• [Presentation] 呼気NO濃度高値が遷延する難治性喘息に対する全身性ステロイド薬の反応性
  • Author(s): 平野綱彦, 松永和人, 岡亜早子, 赤松啓一郎, 南方良章
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜
• [Presentation] Toll様受容体刺激による気道上皮におけるムチン産生およびその機序に関する検討
  • Author(s): 金井一修, 小荒井晃, 杉浦久敏, 市川朋宏, 菊池崇史, 南方良章, 一ノ瀬正和
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
• [Book] COPDの治療戦略～SABAの位置づけ～. 呼吸器疾患のピットフォール (2015)
  • Author(s): 平野綱彦, 一ノ瀬正和
  • Total Pages: 301
  • Publisher: 一般社団法人 呼吸研究
• [Book] 声帯機能不全. 呼吸器疾患のピットフォール (2015)
  • Author(s): 平野綱彦, 一ノ瀬正和
  • Total Pages: 301
  • Publisher: 一般社団法人 呼吸研究
• [Book] 呼吸器疾患のピットフォール（COPDの治療戦略～SABAの位置づけ～） (2015)
  • Author(s): 平野 綱彦、一ノ瀬正和
  • Publisher: 呼吸
• [Book] 呼吸器疾患のピットフォール（声帯機能不全） (2015)
  • Author(s): 平野 綱彦、一ノ瀬正和
  • Publisher: 呼吸
• [Book] COPDへのSABAのアシストユース (2015)
  • Author(s): 平野 綱彦
  • Publisher: PROGRESS IN MEDICINE
• [Book] イラストでわかる呼吸器内科学（呼吸器内視鏡） (2014)
  • Author(s): 一ノ瀬正和著 平野綱彦
  • Publisher: 文光堂
• [Book] ステロイド薬使用に伴う副作用とその対策 (2014)
  • Author(s): 佐野綾香, 平野綱彦, 松永和人
  • Publisher: 呼吸
• [Book] COPD治療におけるコンビネーションセラピー 病態理解から最新治療まで（夜間低換気のあるCOPD症例に対する併用療法） (2014)
  • Author(s): 平野 綱彦
  • Publisher: 医薬ジャーナル社
• [Book] 気道炎症の差異と呼気一酸化窒素濃度 (2014)
  • Author(s): 平野 綱彦
  • Publisher: アレルギー・免疫
• [Book] COPDと喘息の合併. 二人三脚 喘息診療 (2013)
  • Author(s): 平野綱彦, 松永和人
  • Total Pages: 9
  • Publisher: 日本医事新報
• [Remarks] 研究業績の紹介
  • URL: http://www.kokyuki.med.yamaguchi-u.ac.jp/research/