The role of Proton-sensing ovarian cancer G protein-coupled receptor 1 in a murine asthma model.

• Project/Area Number: 25860635
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Gunma University
• Principal Investigator: AOKI HARUKA 群馬大学, 生体調節研究所, 助教 (80447268)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 気管支喘息 / アレルギー / アレルギー・ぜんそく / 樹状細胞

Outline of Final Research Achievements

OGR1 stimulation by extracellular protons causes the activation of G proteins and subsequent cellular functions. In the present study, we show that OGR1-deficient mice are resistant to the cardinal features of asthma, including airway eosinophilia, airway hyperresponsiveness, and goblet cell metaplasia, in association with a remarkable inhibition of Th2 cytokine and IgE productionl. Intratracheal transfer to wild-type mice of OVA-primed bone marrow-derived dendritic cells (DCs) from OGR1-deficient mice developed lower AHR and eosinophilia after OVA inhalation compared with the transfer of those from wild-type mice. Migration of OVA-pulsed DCs to peribronchial lymph nodes was also inhibited by OGR1 deficiency in the adoption experiments. OVA-induced expression of CCR7, a mature DC chemokine receptor, and migration response to CCR7 ligands in an in vitro Transwell assay were attenuated by OGR1 deficiency.

Research Products

• [Journal Article] Protective role of proton-sensing TDAG8 in lipopolysaccharide-induced acute lung injury. (2015)
  • Author(s): H. Tsurumaki, C. Mogi, H. Aoki-Saito, M. Tobo, Y. Kamide, M. Yatomi, K. Sato, K. Dobashi, T. Ishizuka, T. Hisada, M. Yamada, F. Okajima
  • Journal Title: Int. J. Mol. Sci. Volume: 16 Issue: 12 Pages: 28931-28942
  • DOI: 10.3390/ijms161226145
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 17(R)-resolvin D1 ameliorates bleomycin-induced pulmonary fibrosis in mice. (2015)
  • Author(s): Yatomi M, Hisada T, Ishizuka T, Koga Y, Ono A, Kamide Y, Seki K, Aoki-Saito H, Tsurumaki H, Sunaga N, Kaira K, Dobashi K, Yamada M, Okajima F.
  • Journal Title: PHYSIOLOGICAL REPORTS Volume: 3 Issue: 12 Pages: 12628-12628
  • DOI: 10.14814/phy2.12628
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells (2015)
  • Author(s): Y. Kamide, T. Ishizuka, M. Tobo, H. Tsurumaki, H. Aoki, C. Mogi, T. Nakakura, M. Yatomi, A. Ono, Y. Koga, K. Sato, T. Hisada, K. Dobashi, M. Yamada, F. Okajima
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 464 Issue: 3 Pages: 949
  • DOI: 10.1016/j.bbrc.2015.07.077
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Safety and efficacy of high-dose leukocytapheresis in patients with refractory asthma. (2014)
  • Author(s): Ishizuka T, Hisada T, Hatori M, Koike A, Hanabuchi K, Matsuzaki S, Kamide Y, Utsugi M, Aoki H, Yoshino R, Yanagitani N, Koga Y, Ono A, Kaira K, Sunaga N, Dobashi K, Tsuburai T, Akiyama K, Yamada M, Suzuki K, Mori M.
  • Journal Title: Inflammation Research. Volume: Sep;63(9) Issue: 9 Pages: 789-96
  • DOI: 10.1007/s00011-014-0753-1
  • Peer Reviewed
• [Journal Article] Acidic pH increases cGMP accumulation through the OGR1/phospholipase C/Ca2+/neuronal NOS pathway in N1E-115 neuronal cells. (2014)
  • Author(s): M. Kotake, K. Sato, C. Mogi, M. Tobo, H. Aoki, T. Ishizuka, N. Sunaga, H. Imai, K. Kaira, T. Hisada, M. Yamada, F. Okajima
  • Journal Title: Cell. Signal. Volume: 26 Issue: 11 Pages: 2326-2332
  • DOI: 10.1016/j.cellsig.2014.07.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ionotropic and metabotropic proton-sensing receptors involved in airway inflammation in allergic asthma. (2014)
  • Author(s): Aoki H, Mogi C, Okajima F.
  • Journal Title: Mediators Inflamm. Volume: 712962 Pages: 712962-712962
  • DOI: 10.1155/2014/712962
  • Peer Reviewed / Open Access
• [Journal Article] The effects of concomitant GERD, dyspepsia, and rhinosinusitis on asthma symptoms and FeNO in asthmatic patients taking controller medications. (2014)
  • Author(s): Ishizuka T, Hisada T, Kamide Y, Aoki H, Seki K, Honjo C, Sakai H, Kadowaki M, Umeda Y, Morikawa M, Anzai M, Ameshima S, Ishizaki T, Dobashi K, Yamada M, Kusano M.
  • Journal Title: Journal of Asthma and Allergy Volume: Sep 5;7: Pages: 131-9
  • DOI: 10.2147/jaa.s67062
  • Peer Reviewed / Open Access
• [Journal Article] Proton-sensing ovarian cancer G protein-coupled receptor 1 on dendritic cells is required for airway responses in a murine asthma model (2013)
  • Author(s): Aoki H, Mogi C, Hisada T, Kamide Y, Ichimonji I, Tomura H, Tobo M, Sato K, Tsurumaki H, Dobashi K, Mori T, Harada H, Yamada M, Mori M, Ishizuka T, Okajima F
  • Journal Title: PLoS ONE Volume: 8 Issue: 11 Pages: e79985-e79985
  • DOI: 10.1371/journal.pone.0079985
  • Peer Reviewed
• [Presentation] ハウスダストマイト点鼻気管支喘息モデルにおけるプロトン感知性受容体OGR1の役割 (2016)
  • Author(s): 齋藤（青木）悠、茂木千尋、鶴巻寛朗、矢冨正清、上出庸介、古賀康彦、小野昭浩、土橋邦生、石塚全、岡島史和、久田剛志
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2016-06-18
• [Presentation] T細胞におけるプロトン感知性受容体OGR1の役割 (2016)
  • Author(s): 齋藤（青木）悠、茂木千尋、鶴巻寛朗、久田剛志、小野昭浩、古賀康彦、関香織、矢冨正清、上出庸介、土橋邦生、石塚全、山田正信、岡島史和
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2016-04-08
• [Presentation] Critical role of proton-sensing OGR1 in dendritic cells in development of asthma (2014)
  • Author(s): Haruka Aoki, Takeshi Hisada, Chihiro Mogi, Masakiyo Yatomi, Hiroaki Tsurumaki, Yosuke Kamide, Akihiro Ono, Yasuhiko Koga, Kunio Dobashi, Tamotsu Ishizuka, Masanobu Yamada and Fumikazu Okajima
  • Organizer: ERS Annual Congress Munich 2014
  • Place of Presentation: ミュンヘン（ドイツ）
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] アレルギー疾患モデルからの最新知見 (2014)
  • Author(s): 青木 悠
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 国立京都国際会館（京都府）
  • Year and Date: 2014-05-09 – 2014-05-11
  • Invited
• [Presentation] Proton-sensing OGR1 on dendritic cell is required for airway responses in a murine asthma model (2014)
  • Author(s): 青木 悠，茂木千尋，久田剛志，砂長則明，古賀康彦，小野昭浩，解良恭一，上出庸介，関 香織，矢冨正清，鶴巻寛朗，小竹美絵，西岡正樹，笠原礼光，土橋邦生，山田正信、石塚 全，岡島史和
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] Relevance of Hemoglobin A1c and Acute Exacerbations of Chronic Obstructive Pulmonary Disease (2014)
  • Author(s): Haruka Aoki, Takeshi Hisada, Yasuhiko Koga, Akihiro Ono, Hiroaki Tsurumaki, Yosuke Kamide, Masaki Nishioka, Kunio Dobashi, Tamotsu Ishizuka, Masanobu Mori
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪国際会議場（大阪）
• [Presentation] Proton-sensing OGR1 on dendritic cell is required for airway (2014)
  • Author(s): 青木 悠、茂木千尋、久田剛志、砂長則明、古賀康彦、小野昭浩、解良恭一、上出庸介、関 香織、矢冨正清、鶴巻寛朗、小竹美絵、西岡正樹、笠原礼光、土橋邦生、山田正信、石塚 全、岡島史和
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪国際会議場（大阪）
• [Presentation] 気管支喘息モデルにおけるプロトン感知性受容体OGR1の役割 (2014)
  • Author(s): 青木 悠、茂木千尋、久田剛志、古賀康彦、小野昭浩、関 香織、矢冨正清、上出庸介、鶴巻寛朗、西岡正樹、土橋邦生、森 昌朋、石塚 全、山田正信、岡島史和
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 国立京都国際会館（京都）
  • Invited
• [Presentation] COPD急性増悪とHbA1cの関連性について (2013)
  • Author(s): 青木 悠、久田剛志、石塚 全、鶴巻寛朗、関 香織、矢冨正清、上出庸介、桑原英眞、土橋邦生、森 昌朋
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] Relevance of Hemoglobin A1c and Acute Exacerbations of Chronic Obstructive Pulmonary Disease (2013)
  • Author(s): Haruka Aoki, Takeshi Hisada, Masakiyo Yatomi, Hiroaki Tsurumaki, Reiko Yoshino, Kunio Dobashi, Tamotsu Ishizuka, Masatomo Mori, Masanobu Yamada
  • Organizer: ERS Annual Congress 2013
  • Place of Presentation: バルセロナ（スペイン）
• [Presentation] プロトン感知性受容体OGR1の気管支喘息における役割 (2013)
  • Author(s): 青木 悠、茂木千尋、久田剛志、鶴巻寛朗、上出庸介、中倉 敬、笠原礼光、西岡正樹、関 香織、矢冨正清、小野昭浩、古賀康彦、土橋邦生、石塚 全、山田正信、岡島史和
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: ホテルニューオータニ（東京）
• [Book] 呼吸と循環 (2015)
  • Author(s): 齋藤（青木）悠、岡島史和
  • Total Pages: 6
  • Publisher: 医学書院
• [Book] アレルギーの臨床 (2015)
  • Author(s): 齋藤（青木）悠、岡島史和
  • Total Pages: 4
  • Publisher: 北隆社