The role of proton-sensing G-protein coupled receptors(GPCRs) in the regulation of inflammatory cytokine production during endoscopic surgery

• Project/Area Number: 23591916
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Gunma Institute of Public Health and Environmental Sciences
• Principal Investigator: MURATA Naoya 群馬県衛生環境研究所, 研究企画係, 研究員 (00533473)
• Co-Investigator(Kenkyū-buntansha): OKAJIMA Fumikazu 群馬大学, 生体調節研究所, 教授 (30142748)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: プロトン感知性受容体 / OGR1受容体ファミリー / TDAG8 / 抗炎症性応答 / 実験外科学

Research Abstract

The role of proton-sensing GPCRs in the regulation of lipopolysaccharide(LPS)-induced inflammatory cytokine production was investigated. In vivo injection of LPS into mice resulted in the remarkable accumulation of TNF-alpha. The LPS-induced action tends to be enhanced in the mice deficient in TDAG8 or GPR4; however, the effects of receptor deficiency were not significant. Extracellular acidification inhibited LPS-induced TNF-alpha protein and mRNA production in mouse peritoneal macrophages in vitro. Our results suggest that acidic pH inhibits inflammatory cytokine production at least partly through TDAG8/cAMP/PKA pathways in mouse macrophages.

Research Products

• [Journal Article] Lipoprotein-associated lysolipids are differentially involved in high-density lipoprotein- and its oxidized form-induced neurite remodeling in PC12 cells. (2014)
  • Author(s): Koichi Sato, Masayuki Tobo, Chihiro Mogi, Naoya Murata, Mie Kotake, Atsushi Kuwabara, Dong-Soon Im, Fumikazu Okajima
  • Journal Title: Neurochemistry International Volume: 68 Pages: 38-47
  • DOI: 10.1016/j.neuint.2014.02.005
  • Peer Reviewed
• [Journal Article] Inhibition of interleukin-1β production by extracellular acidification through the TDAG8/cAMP pathway in mouse microglia. (2014)
  • Author(s): Ye Jin, Koichi Sato, Ayaka Tobo, Chihiro Mogi, Masayuki Tobo, Naoya Murata, Satoshi Ishii, Dong-Soon Im and Fumikazu Okajima
  • Journal Title: Journal of Neurochemistry Volume: 129(4) Issue: 4 Pages: 683-695
  • DOI: 10.1111/jnc.12661
  • Peer Reviewed / Open Access
• [Journal Article] Role of extracellular proton-sensing receptors in regulation of insulin secretion and pancreaticβ−cell functions (2014)
  • Author(s): Mogi C, Nakakura T, and Okajima F.
  • Journal Title: Endocrine J. Volume: 61 Pages: 101-110
  • Peer Reviewed
• [Journal Article] Regulation of inflammation by extracellular acidification and proton-sensing GPCRs (2013)
  • Author(s): Okajima F.
  • Journal Title: Cellular Signalling Volume: 25 Issue: 11 Pages: 2263-2271
  • DOI: 10.1016/j.cellsig.2013.07.022
  • Peer Reviewed
• [Journal Article] Oxidative stress potentially enhances FcεRI-mediated leukotriene C_4 release dependent on the late-phase increase of intracellular glutathione in mast cells (2013)
  • Author(s): Seki K, Hisada T, Kawata T, Kamide Y, Dobashi K, Yamada M, Mori M, Okajima F, Ishizuka T
  • Journal Title: Biochem Biophys Res Commun Volume: 439 Issue: 3 Pages: 357-362
  • DOI: 10.1016/j.bbrc.2013.08.081
  • Peer Reviewed
• [Journal Article] Lysophosphatidylethanolamine utilizes LPA1 and CD97 in MDA-MB-231 breast cancer cells (2013)
  • Author(s): Park SJ, Lee KP, Kang S, Chung HY, Bae YS, Okajima F, and Im DS.
  • Journal Title: Cellular Signalling Volume: 25 Issue: 11 Pages: 2147-2154
  • DOI: 10.1016/j.cellsig.2013.07.001
  • Peer Reviewed
• [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
  • URL: https://pure.teikyo.jp/en/publications/43d0a4de-500b-4215-8c43-216e5af1efa1
  • Peer Reviewed
• [Journal Article] Ovarian cancer G-protein-coupled receptor 1 induces the expression of the pain mediator prostaglandin E2 in response to an acidic extracellular environment in human osteoblast-like cells (2012)
  • Author(s): Wang J, Sun Y, Tomura H, Okajima F.
  • Journal Title: Int J Biochem Cell Biol. Volume: 44 Issue: 11 Pages: 1937-1941
  • DOI: 10.1016/j.biocel.2012.07.015
  • Peer Reviewed
• [Journal Article] Deficiency of proton-sensing ovarian cancer G protein-coupled receptor 1 attenuates glucose- stimulated insulin secretion (2012)
  • Author(s): Nakakura T
  • Journal Title: Endocrinology Volume: 153 Issue: 9 Pages: 4171
  • DOI: 10.1210/en.2012-1164
  • Peer Reviewed
• [Journal Article] An orally active lysophosphatidic acid receptor antagonist attenuates panereatic cancer invasion and metastasis in vivo (2012)
  • Author(s): Komachi M
  • Journal Title: Cancer Science Volume: (印刷中) Issue: 6 Pages: 1099-1104
  • DOI: 10.1111/j.1349-7006.2012.02246.x
  • Peer Reviewed
• [Journal Article] Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages (2011)
  • Author(s): Xiao-Dong He
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 415 Issue: 4 Pages: 627
  • DOI: 10.1016/j.bbrc.2011.10.122
  • URL: https://pure.teikyo.jp/en/publications/c087b552-5841-417c-8f3d-ea0c37fa47c1
  • Peer Reviewed
• [Journal Article] Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth musele cells (2011)
  • Author(s): Matsuzaki S
  • Journal Title: Biochem Biophys Res Commun Volume: 413 Issue: 4 Pages: 499-503
  • DOI: 10.1016/j.bbrc.2011.08.087
  • Peer Reviewed
• [Journal Article] Constitutively active heat shock factor 1 enhances glucose-driven insulin secretion (2011)
  • Author(s): Uchiyama T
  • Journal Title: Metabolism Volume: 60 Issue: 6 Pages: 789-798
  • DOI: 10.1016/j.metabol.2010.07.029
  • Peer Reviewed
• [Journal Article] Unmasking of LPA(1)receptor-mediated migration response to lysophosphatidic acid by interleukin-1β-induced attenuation of Rho signaling pathways in rat astrocytes (2011)
  • Author(s): Sato K
  • Journal Title: J Neurochem Volume: 117 Issue: 1 Pages: 164-174
  • DOI: 10.1111/j.1471-4159.2011.07188.x
  • Peer Reviewed
• [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: ホテルニューオオタニ(東京)
• [Presentation] N1E115神経細胞における細胞外酸性pHによるcGMP産生機構 (2013)
  • Author(s): 小竹美絵、佐藤幸市、岡島史和
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(横浜)
• [Presentation] Follow-up of reactivation of HB virus in HBV antibody positive lymphoma after chemotherapy in a single insutitution (2013)
  • Author(s): 五十嵐忠彦、村山佳予子、入沢寛之、村田直哉
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
• [Presentation] 化学療法後に甲状腺の再腫大を認めた甲状腺原発悪性リンパ腫の2例 (2013)
  • Author(s): 村山佳予子、入沢寛之、村田直哉、五十嵐忠彦
  • Organizer: 第53回日本リンパ網内系学会総会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] 化学療法後に甲状腺の再腫大を認めた甲状腺原発悪性リンパ腫の2例 (2013)
  • Author(s): 村山佳予子, 入沢寛之, 村田直哉, 五十嵐忠彦
  • Organizer: 第53回日本リンパ網内系学会総会
  • Place of Presentation: 国立京都国際会館(京都市)
• [Presentation] Follow-up of reactivation of HB virus in HBV antibody positive lymphoma after chemotherapy in a single institution (2013)
  • Author(s): 五十嵐忠彦, 村山佳予子, 入沢寛之, 村田直哉
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台国際センタ－(宮城県仙台市)
• [Presentation] プロトン感知性OGR1ファミリ-GPCRとその機能 (2012)
  • Author(s): 岡島史和
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] 膵β細胞におけるプロトン感知性OGR1を介したインスリン分泌シグナルの解析 (2012)
  • Author(s): 中倉敬、茂木千尋、戸村秀明、岡島史和
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] Involvement of TDAG8 in extracellular acidification-induced inhibition of interleukin-1beta production in microglia (2012)
  • Author(s): Ye Jin, Koichi Sato, Fumikazu Okajima
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] N1E115神経細胞における細胞外酸性pHによる細胞内Ca2+動員、Aktリン酸化とプロトン感知性受容体の関与 (2012)
  • Author(s): 佐藤幸市、小竹美絵、岡島史和
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  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] プロトンはマウス肥満細胞からのサイトカイン産生を調節する (2012)
  • Author(s): 上出庸介、石塚全、鶴巻寛朗、山下均、山田秀典、宇津木光克、小野昭浩、古賀康彦、久田剛志、土橋邦生、岡島史和、森昌朋
  • 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)
• [Presentation] プロトン感知性Gタンパク質共役型受容体OGR1KOマウスにおける気管支喘息モデルの解析 (2012)
  • Author(s): 青木悠、茂木千尋、久田剛志、石塚全、上出庸介、鶴巻寛朗、土橋邦生、岡島史和、森昌朋
  • 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)
• [Presentation] Primary malignant lymphoma of the breast presenting a huge inflammatory breast mass (2012)
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  • Organizer: 第74回日本血液学会学術集会
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• [Presentation] Incidence and outcome of the infectious diseases after MEAM therapy with autoPBSCT for lymphoma (2012)
  • Author(s): Kayoko Murayama, Hiroyuki Irisawa, Naoya Murata, Tadahiko Igarashi
  • Organizer: 第74回日本血液学会学術集会
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• [Presentation] A case of Enteropathy-associated T-cell lymphoma(EATL) complicating CLL/SLL (2012)
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  • Organizer: 第74回日本血液学会学術集会
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• [Presentation] ヒト膵臓がん細胞の浸潤・転移に対する経口可能なリゾホスファチジン酸受容体アンタゴニストKi16198の抑制作用 (2012)
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• [Presentation] Feasibility of MEAM therapy with autologous stem cell transplant for high-risk/relapsed lymphoma (2011)
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• [Presentation] Diffuse large B cell lymphoma(DLBCL) of stomach with fatal Edwardsiella tarda sepsis (2011)
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  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場(名古屋)