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Identification of palmitoylethanolamide and oleoylethanolamide with inhibitory effect on SLE-related inflammation

Research Project

Project/Area Number 18K16155
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionOita University

Principal Investigator

Ozaki Takashi  大分大学, 医学部, 助教 (70749374)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsパルミトイルエタノールアミド / Toll様受容体 / 脂質メディエーター / オレオイルエタノールアミド / パルミトイルエタノールアミド 容体 / Toll様受容体9 / SLE / 炎症
Outline of Final Research Achievements

Palmitoylethanolamide (PEA), an endogenous N-acylethanolamide, can suppress inflammation induced by Toll-like receptor (TLR) signaling both in vitro and in vivo. PEA suppressed pro-inflammatory cytokine production in a mouse macrophage cell line (RAW 264.7) in response to TLR ligands such as lipopolysaccharide, peptidoglycan, poly (I:C), imiquimod and CpG-ODN. PEA inhibited both mRNA and protein levels of IL-6 in bone marrow derived dendritic cells (BMDCs) and B cells stimulated with CpG-ODN. In addition, co-stimulatory molecules such as CD80 and CD40 on BMDCs and B cells, together with IgM production and cell proliferation of B cells, were attenuated by PEA. Moreover, PEA significantly reduced mortality and serum IL-6 levels in mice injected with CpG-ODN plus D-galactosamine. Taken together, these results suggest that PEA ameliorates inflammation by inhibiting TLR signaling, which could be a novel therapeutic target for inflammatory disorders.

Academic Significance and Societal Importance of the Research Achievements

近年、抗炎症性の脂質メディエーターが注目される中において、本研究を通じてパルミトイルエタノールアミド(PEA)が各種免疫担当細胞におけるTLR9刺激を介した炎症性サイトカイン産生や細胞表面マーカー発現、細胞増殖や抗体産生に対していずれも抑制的に作用することが明らかとなった。また、PEAの抗炎症作用はSeptic shockモデルマウスの生体内においても発揮されることも見出した。将来的にSLEをはじめとするTLRが関連した炎症性疾患の治療薬として、PEAが創薬のターゲットとなり得る可能性が示唆される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (11 results) Book (1 results)

  • [Journal Article] Effectiveness of subcutaneous tocilizumab in refractory adult Still’s disease: report of three cases and a review of the literature2021

    • Author(s)
      Torigoe Masataka、Maeshima Keisuke、Kuriyama Yuhei、Abe Itomi、Ozaki Takashi、Omura Yuichi、Umeki Tatsuhito、Imada Chiharu、Ishii Koji、Shibata Hirotaka
    • Journal Title

      Modern Rheumatology Case Reports

      Volume: 5 Issue: 2 Pages: 1-6

    • DOI

      10.1080/24725625.2021.1886402

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] l-Leucine influx through Slc7a5 regulates inflammatory responses of human B cells via mammalian target of rapamycin complex 1 signaling2019

    • Author(s)
      Torigoe Masataka、Maeshima Keisuke、Ozaki Takashi、Omura Yuichi、Gotoh Koro、Tanaka Yoshiya、Ishii Koji、Shibata Hirotaka
    • Journal Title

      Modern Rheumatology

      Volume: 29 Issue: 5 Pages: 885-891

    • DOI

      10.1080/14397595.2018.1510822

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Sleeve Gastrectomy on Blood Pressure and the Renal Renin-Angiotensin System in Rats with Diet-Induced Obesity.2019

    • Author(s)
      Yoshida Y, Gotoh K, Masaki T, Ozeki Y, Tokoro M, Kudo A, Ozaki T, Okamoto M, Chiba S, Watanabe K, Ohta M, Inomata M, Shibata H.
    • Journal Title

      Obesity (Silver Spring)

      Volume: 27 Issue: 5 Pages: 785-792

    • DOI

      10.1002/oby.22443

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral administration of antibiotics results in fecal occult bleeding due to metabolic disorders and defective proliferation of the gut epithelial cell in mice2018

    • Author(s)
      Sonoda Akira、Kamiyama Naganori、Ozaka Sotaro、Gendo Yoshiko、Ozaki Takashi、Hirose Haruna、Noguchi Kaori、Saechue Benjawan、Sachi Nozomi、Sakai Kumiko、Mizukami Kazuhiro、Hidano Shinya、Murakami Kazunari、Kobayashi Takashi
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 12 Pages: 1043-1055

    • DOI

      10.1111/gtc.12649

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Autoimmune sialadenitis is associated with the upregulation of chemokine/chemokine receptor pairs in T cell-specific TRAF6-deficient mice2018

    • Author(s)
      Noguchi Kaori、Kamiyama Naganori、Hidano Shinya、Gendo Yoshiko、Sonoda Akira、Ozaki Takashi、Hirose Haruna、Sachi Nozomi、Saechue Benjawan、Ozaka Sotaro、Eshita Yuki、Mizukami Kazuhiro、Kawano Kenji、Kobayashi Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 504 Issue: 1 Pages: 245-250

    • DOI

      10.1016/j.bbrc.2018.08.162

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dysbiosis of the Gut Microbiota on the Inflammatory Background due to Lack of Suppressor of Cytokine Signalling-1 in Mice2018

    • Author(s)
      Gendo Y、Matsumoto T、Kamiyama N、Saechue B、Fukuda C、Dewayani A、Hidano S、Noguchi K、Sonoda A、Ozaki T、Sachi N、Hirose H、Ozaka S、Eshita Y、Mizukami K、Okimoto T、Kodama M、Yoshimatsu T、Nishida H、Daa T、Yamaoka Y、Murakami K、Kobayashi T
    • Journal Title

      Inflammatory Intestinal Diseases

      Volume: 3 Issue: 3 Pages: 145-154

    • DOI

      10.1159/000495462

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 急速進行性の間質性肺炎と多彩な神経精神症状を呈した抗MDA5抗体陽性皮膚筋炎の一例2021

    • Author(s)
      尾崎貴士, 首藤航太, 新貝祐太, 児玉尚吾, 梅木達仁, 大村雄一, 今田千晴, 堀田美鈴, 安倍いとみ, 森山かおり, 前島圭佑, 石井宏治, 柴田洋孝
    • Organizer
      第61回九州リウマチ
    • Related Report
      2020 Annual Research Report
  • [Presentation] 再燃を繰り返す多発性筋炎に生物学的製剤多剤抵抗性の関節リウマチを合併し、治療に苦慮した一例2021

    • Author(s)
      今田千晴, 児玉尚吾, 清永恭弘, 立川裕史, 尾崎貴士, 石井宏治, 柴田洋孝
    • Organizer
      第61回九州リウマチ
    • Related Report
      2020 Annual Research Report
  • [Presentation] A comprehensive LC-MS/MS lipid mediator analysis of lupus-prone mice revealed inhibitory effects of palmitoylethanolamide on Toll-like receptor 9-mediated inflammation2019

    • Author(s)
      Takashi Ozaki, Keisuke Maeshima, Koji Ishii, Hirotaka Shibata, Takashi Kobayashi
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 難治性急速進行性間質性肺炎に対しリツキシマブが奏功した抗MDA5抗体陽性皮膚筋炎の一例2019

    • Author(s)
      児玉尚吾、梅木達仁、大村雄一、鳥越雅隆、尾崎貴士、今田千晴、前島圭佑、石井宏治、柴田洋孝
    • Organizer
      第63回日本リウマチ学会総会・学術集
    • Related Report
      2019 Research-status Report
  • [Presentation] リツキシマブとミコフェノール酸モフェチルとタクロリムスの併用療法により寛解導入し得たステロイド抵抗性好酸球性多発血管炎性肉芽腫症の一例2019

    • Author(s)
      新貝 祐太、梅木 達仁、安部 佑、児玉 尚吾、尾崎 貴士、安部 いとみ、前島 圭佑、石井 宏治、柴田 洋孝
    • Organizer
      第58回九州リウマチ学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of a rapid and simple reverse transcription loop-mediated isothermal amplification for Chikungunya virus2018

    • Author(s)
      Benjawan Saechue, Naganori Kamiyama, Shinya Hidano, Kaori Noguchi, Yoshiko Gendo, Takashi Ozaki,  Akira Sonoda, Haruna Hirise, Nozomi Sachi, Sotaro Ozaka, Takashi Kobayashi
    • Organizer
      41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] アフリカ株とアジア株SRIPsを用いた、ジカウイルスの宿主細胞侵入効率の解析2018

    • Author(s)
      神山長慶, 渡辺 景, Benjawan Saechue, 飛彈野真也, 野口香緒里, 玄同淑子, 尾崎貴士, 園田光, 広瀬 晴奈, 小坂 聡太郎, 佐知望美, 鈴木 亮介, 小林隆志
    • Organizer
      41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 可溶性インターロイキン2受容体の全身性エリテマトーデスにおけるバイオマーカーとしての有用性の検討2018

    • Author(s)
      大村雄一、前島圭佑、梅木達仁、清永恭弘、鳥越雅隆、今田千晴、尾崎貴士、堀田美鈴、安倍いとみ、熊木美登里、石井宏治、柴田洋孝
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 急速に進行する皮膚硬化を呈した全身性強皮症に対し,トシリズマブ(TCZ)が著効したと考えられる一例2018

    • Author(s)
      今田千晴、梅木達仁、大村雄一、鳥越雅隆、尾崎貴士、前島圭佑、石井宏治、柴田洋孝
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 不明熱を呈した抗PL-12抗体陽性抗ARS抗体症候群の1例2018

    • Author(s)
      福田春菜、梅木達仁、大村雄一、鳥越雅隆、尾崎貴士、今田千晴、前島圭佑、加島尋、堀之内登、宮崎英士、石井宏治、柴田洋孝
    • Organizer
      第322回 日本内科学会九州地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] トシリズマブが有効であった蛋白漏出性胃腸症合併全身性エリテマトーデスの一症例2018

    • Author(s)
      児玉尚吾、今田千晴、前島圭佑、梅木達仁、大村雄一、鳥越雅隆、尾崎貴士、石井宏治、柴田洋孝
    • Organizer
      第56回九州リウマチ
    • Related Report
      2018 Research-status Report
  • [Book] レジデントノート増刊 日常診療の質が上がる新常識 「生物学的製剤の新常識(関節リウマチの治療を中心に)」2020

    • Author(s)
      尾崎貴士、 柴田洋孝
    • Total Pages
      12
    • Publisher
      羊土社
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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