Understanding for the pathogenic mechanisms of NOX1 expressed in macrophages in intestinal inflammation

• Project/Area Number: 25460110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Kato Shinichi 京都薬科大学, 薬学部, 教授 (90281500)
• Co-Investigator(Kenkyū-buntansha): IWATA Kazumi 京都府立医科大学, 医学(系)研究科(研究院), 講師 (60305571)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: NOX1 / 活性酸素 / マクロファージ / 消化管炎症 / サイトカイン / ケモカイン / 腸管マクロファージ

Outline of Final Research Achievements

The aim of the present study is to clarify the pathogenic role of NOX1 in colonic inflammation. We showed that 1) NOX1 plays detrimental roles in the pathogenesis of TNBS-induced colitis accompanied by various inflammatory responses; 2) NOX1 is expressed in macrophages located in lamina propria of colon; 3) NOX1 expressed in macrophages regulates the expression of cytokines and chemokine in response to inflammatory stimuli. These findings suggest that NOX1 expressed in colonic macrophages is involved in the pathogenesis of colonic inflammation via up-regulation of inflammatory cytokines and chemokines.

Research Products

• [Journal Article] Role of NADPH oxidase 1 (NOX1) in gut inflammation (2016)
  • Author(s): 加藤伸一
  • Journal Title: Folia Pharmacologica Japonica Volume: 147 Issue: 1 Pages: 18-22
  • DOI: 10.1254/fpj.147.18
  • NAID: 130005118584
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed
• [Journal Article] Serotonin/5-hydroxytryptamine-3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis (2016)
  • Author(s): Utsumi D, Matsumoto K, Amagase K, Horie S, Kato S.
  • Journal Title: Br. J. Pharmacol., Volume: 173 Issue: 11 Pages: 1835-1849
  • DOI: 10.1111/bph.13482
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Saireito (TJ-114), a Japanese traditional herbal medicine, reduces 5-fluorouracil-induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in intestinal crypt cells. (2015)
  • Author(s): Kato S, Hayashi, S, Kitahara Y, Nagasawa K, Aono H, Shibata J, Utsumi D, Amagase K, Kadowaki M
  • Journal Title: Plos One Volume: 10 Issue: 1 Pages: e0116213-e0116213
  • DOI: 10.1371/journal.pone.0116213
  • Peer Reviewed / Open Access
• [Presentation] 炎症性腸疾患の病態におけるNOX1/NADPH oxidase の役割 (2015)
  • Author(s): 續木彩香、島田裕規、今井梓嵯、岩田和美、矢部千尋、加藤伸一
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2015
  • Place of Presentation: 東京
  • Year and Date: 2015-08-29
• [Presentation] Serotonin/5-HT3 receptor and substance P/NK1 receptor pathways contribute to the pathogenesis of colonis inflammation in mice. (2015)
  • Author(s): Daichi Utsumi, Kenjiro Matsumoto, Kikuko Amagase, Shinichi Kato
  • Organizer: Digestive Disease Week 2015
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2015-05-19
  • Int'l Joint Research
• [Presentation] 炎症性腸疾患の病態におけるNADPH oxdase 1（NOX1）の役割 (2015)
  • Author(s): 加藤伸一
  • Organizer: 第88回日本薬理学会年会 シンポジウム24
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-19
  • Invited
• [Presentation] トリニトロベンゼンスルホン酸(TNBS)誘起大腸炎の病態における NADPH oxidase 1 (NOX1)の役割 (2014)
  • Author(s): 今井梓嵯、上田伸幸、横田 遥1、岩田和実、松本健次郎、天ヶ瀬紀久子、矢部千尋、加藤伸一
  • Organizer: 生体機能と創薬シンポジウム2014
  • Place of Presentation: 近畿大学
  • Year and Date: 2014-08-28
• [Presentation] NADPH oxidase (NOX1) expressed in colonic macrophages plays a crucial role in trinitrobenzene sulfonic acid (TNBS)-induced clonic inflammation in mice. (2014)
  • Author(s): Yokota, H, Utsumi D, Nakajima H, Tanaka R, Yamada M, Tanaka Y, Amagase K, Kato S
  • Organizer: Digestive Diseases Week 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-05-03 – 2014-05-06
• [Presentation] NADPH Oxidase 1 (NOX1) Expressed in Colonic Macrophages Plays a Crucial Role in Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colonic Inflammation in Mice. (2014)
  • Author(s): Haruka Yokota, Daichi Utsumi, Hiroyo Nakajima, Riho Tanaka, Mari Yamada, Yuya Tanaka, Kikuko Amagase, Shinichi Kato
  • Organizer: Digestive Diseases Week 2014
  • Place of Presentation: Chicago, USA
• [Presentation] トリニトロベンゼンスルホン酸（TNBS）誘起大腸炎の病態におけるNADPH oxidase1(NOX1)の役割 (2013)
  • Author(s): 加藤伸一、天ヶ瀬紀久子、竹内孝治
  • Organizer: 日本潰瘍学会
  • Place of Presentation: 大阪
• [Funded Workshop] Digestive Disease Week 2015 (2015)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2015-05-16