Identification of novel atopic dermatitis biomarkers by lipidomic analysis

• Project/Area Number: 21590599
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: NAKAMURA Mitsuhiro 岐阜薬科大学, 薬学部, 准教授 (30433204)
• Co-Investigator(Kenkyū-buntansha): INAGAKI Naoki 岐阜薬科大学, 薬学部, 教授 (30137062) ; BANNO Yoshiko 岐阜大学, 医学系研究科, 非常勤講師 (50116852)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: シグナル伝達 / 脂質 / アレルギー・喘息 / 薬理学 / 分析化学 / アトピー性皮膚炎 / バイオマーカー / 質量分析 / アレルギー・ぜんそく

Research Abstract

Sphingolipid metabolites such as ceramides, major lipids of the stratum corneum, are known to play critical roles in various epidermal functions. Patients with atopic dermatitis commonly show reduced ceramide contents of the skin.
We developed several mass spectrometry methods(LC-MS/MS, MALDI-TOF, and LC/MS-IT-TOF) for the rapid, simultaneous quantification of C_<16>-, C_<18>-, C_<20>-, C_<22>-, C_<24>-, and C_<24>:_<1>-ceramide. This method was successfully applied to monitor the profiles of fatty acid lengths of ceramides in the stratum corneum. The profiles of fatty acid lengths of ceramides could be useful for the diagnosis of atopic dermatitis.

Research Products

• [Journal Article] <i>Lactobacillus acidophilus</i> Strain L-92 Induces CD4⁺CD25⁺Foxp3⁺ Regulatory T Cells and Suppresses Allergic Contact Dermatitis (2012)
  • Author(s): Shah M. M., Saio M., Yamashita H., Tanaka H., Takami T., Ezaki T., Inagaki N.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 35 Issue: 4 Pages: 612-616
  • DOI: 10.1248/bpb.35.612
  • NAID: 130001872213
  • ISSN: 0918-6158, 1347-5215
• [Journal Article] The pivotal role of intracellular calcium in oxaliplatin-induced inhibition of neurite outgrowth but not cell death in differentiated PC12 cells (2011)
  • Author(s): Takeshita M., Banno Y., Nakamura M., Otsuka M., Teramachi H., Tsuchiya T., Itoh Y.
  • Journal Title: Chem. Res. Toxicol Volume: 24 Issue: 11 Pages: 1845-1852
  • DOI: 10.1021/tx200160g
• [Journal Article] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines (2011)
  • Author(s): Ito H., Yoshida K., Murakami M., Hagiwara K., Sasaki N., Kobayashi M., Takagi A., Kojima T., Sobue S., Suzuki M., Tamiya-Koizumi K., Nakamura M., Banno Y., Nozawa Y., Murate T.
  • Journal Title: Biochim. Biophys. Acta Volume: 1811 Issue: 3 Pages: 119-128
  • DOI: 10.1016/j.bbalip.2010.12.005
  • Peer Reviewed
• [Journal Article] The pivotal role of intracellular calcium in oxaliplatin-induced inhibition of neurite outgrowth but not cell death in differentiated PC12 cells (2011)
  • Author(s): Takeshita M., et al
  • Journal Title: Chem Res Toxicol Volume: 24 Pages: 1845-1852
  • Peer Reviewed
• [Journal Article] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines (2011)
  • Author(s): H.Ito, et al.
  • Journal Title: Biochim Biophys Acta Volume: 1811 Pages: 119-128
  • Peer Reviewed
• [Journal Article] Analyses of benzodiazepines and their metabolites in various biological matrices by LC-MS(/MS) (2011)
  • Author(s): M.Nakamura
  • Journal Title: Biomed Chromatogr Volume: 25
  • Peer Reviewed
• [Journal Article] Orally supplemented Lactobacillus acidophilus strain L-92 inhibits passive and active cutaneous anaphylaxis as well as 2, 4-dinitrofluorobenzene and mite fecal antigen induced atopic dermatitis-like ski lesions in mice (2010)
  • Author(s): Shah M. M., Miyamoto Y., Yamada Y., Yamashita H., Tanaka H., Ezaki T., Nagai H., Inagaki N.
  • Journal Title: Microbiol. Immunol Volume: 54 Issue: 9 Pages: 523-533
  • DOI: 10.1111/j.1348-0421.2010.00251.x
• [Journal Article] Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of dinitrofluorobenzene-induced atopic dermatitis (2010)
  • Author(s): Yamashita H., Ito T., Kato H., Asai S., Tanaka H., Nagai H., Inagaki N.
  • Journal Title: Eur. J. Pharmacol Volume: 645 Issue: 1-3 Pages: 171-176
  • DOI: 10.1016/j.ejphar.2010.07.031
• [Journal Article] Depletion of substance P, a mechanism for inhibition of mouse scratching behavior by tacrolimus (2010)
  • Author(s): Inagaki N., Shiraishi N., Igeta K., Nagao M., Kim J. F., Chikumoto T., Itoh T., Katoh H., Tanaka H., Nagai H.
  • Journal Title: Eur. J. Pharmacol Volume: 626 Issue: 2-3 Pages: 283-289
  • DOI: 10.1016/j.ejphar.2009.09.043
• [Journal Article] Sphingosine kinase isoforms regulate oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and AKT activtion (2009)
  • Author(s): Nemoto S., Nakamura M., Osawa Y., Kono S., Itoh Y., Okano Y., Murate T., HaraA., Ueda H., Nozawa Y., Banno Y.
  • Journal Title: J. Biol. Chem Volume: 284 Issue: 16 Pages: 10422-10432
  • DOI: 10.1074/jbc.m900735200
• [Journal Article] Sphingosine kinase isoforms regulate oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and AKT activation (2009)
  • Author(s): Nenito S., et al.
  • Journal Title: J.Biol.Chem 284 Pages: 10422-10432
  • Peer Reviewed
• [Journal Article] Simultaneous determination of benzodiazepines and their metabolites in human serum by liquid chromatography-tandem mass spectrometry using a high resolution octadecyl silica column compatible with aqueous compo unds (2009)
  • Author(s): Nakamura M., et al.
  • Journal Title: Biomed Chromatogr 23 Pages: 357-364
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin (2009)
  • Author(s): Ito H., et al.
  • Journal Title: Biochim Biophys Acta. 1789 Pages: 681-690
  • Peer Reviewed
• [Journal Article] ATRA inhibits ceramide kinase transcription in a human neuroblastoma cell line, SH-SY5Y cells : the role of COUP-TFI (2009)
  • Author(s): Murakami M., et al.
  • Journal Title: J Neurochem 112 Pages: 511-520
  • Peer Reviewed
• [Journal Article] Characterization of skin inflammation induced by repeated exposure of toluene, xylene, and formaldehyde in mice (2009)
  • Author(s): Saito A., et al.
  • Journal Title: Environ Toxicol. (Epub ahead of print)
  • Peer Reviewed
• [Presentation] LCMS-IT-TOFによるスフィンゴ脂質測定系の開発 (2012)
  • Author(s): 西端友里、中村光浩、伊藤裕美、大塚万祐子、小泉恵子、土屋照雄、村手隆、坂野喜子
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] LCMS-IT-TOFによるスフィンゴシン脂質測定系の開発 (2012)
  • Author(s): 中材光浩, ら
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] The effect on acid sphingomyelinase(ASMase) by resveratrol (2011)
  • Author(s): 伊藤裕美、萩原和美、田中広治、小林美沙、星川あすか、水谷直貴、高木明、小嶋哲人、小泉恵子、中村光浩、坂野喜子、野澤義則、村手隆
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] The effect on acid sphingomyelinase (ASMase) by resveratrol (2011)
  • Author(s): 伊藤裕美, ら
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Sphingosine Kinase Regulate Oxaliplatin Sensitivity of Human Colon Cancer Cells through Ceramide Accumulation and CD44 expression (2010)
  • Author(s): Kawahara S., Nakamura M., Murate T., Hara A., Nozawa Y., and Banno Y.
  • Organizer: 51st International Conference on the Bioscience of Lipids
  • Place of Presentation: Bilbao, Spain
• [Presentation] The regulatory mechanism of NSMase2 gene expression by ATRA in MCF7 cells (2010)
  • Author(s): Ito H., Murakami M., Hagiwara K., Sasaki N., Kobayashi M., Hoshikawa A., Takagi A., Kojima T., Banno Y., Tamiya-Koizumi K., Nakamura M., Nozawa Y., Murate T.
  • Organizer: 51st International Conference on the Bioscience of Lipids
  • Place of Presentation: Bilbao, Spain
• [Presentation] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines (2010)
  • Author(s): Murate1 T., Yoshida K., Ito H., Murakami M., Hagiwara K., Tagawa Y., Sasaki N., Takagi A., Kojima T., Sobue S., Suzuki M., Tamiya-Koizumi K., Nakamura M., Banno Y., Nozawa Y.
  • Organizer: 51st International Conference on the Bioscience of Lipids
  • Place of Presentation: Bilbao, Spain
• [Presentation] シスプラチンによる神経細胞様PC12細胞の突起退縮に対するデセン酸の効果 (2010)
  • Author(s): 大塚万祐子、中村光浩、川原さと実、竹下未希、原明、坂野喜子、土屋照雄
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] スフィンゴ脂質代謝による抗癌剤感受性とCD44発現の調節機構 (2010)
  • Author(s): 川原さと実、中村光浩、大辻陽子、原明、村手隆、野澤義則、坂野喜子
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] Down regulation of neutral ceramidase induces neural differentiation in human neuroblastoma SH-SY5Y cells (2010)
  • Author(s): Tanaka K., Tamiya-Koizumi K., Hagiwara K., Murakami M., Murate T., Banno Y., Nakamura M., Kannagi R., Kyogashima M.
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] Sphingosine Kinase Regulate Oxaliplatin Sensitivity of Human Colon Cancer Cells through Ceramide Accumulation and CD44 expression (2010)
  • Author(s): S Kawahara, et al.
  • Organizer: 51^<st> International Conference on the Bioscience of Lipids
  • Place of Presentation: Spain
• [Presentation] The regulatory mechanism of NSMase2 gene expression by ATRA in MCF7 cells (2010)
  • Author(s): H.Ito, et al.
  • Organizer: 51^<st> International Conference on the Bioscience of Lipids
  • Place of Presentation: Spain
• [Presentation] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines (2010)
  • Author(s): T.Murate, et al.
  • Organizer: 51^<st> International Conference on the Bioscience of Lipids
  • Place of Presentation: Spain
• [Presentation] 大腸癌細胞のスフィンゴ脂質代謝による抗癌剤感受性の制御機構 (2009)
  • Author(s): 河野早紀、竹下未希、根本聡、中村光浩、伊藤善規、土屋照雄、村手隆、野澤義則、坂野喜子
  • Organizer: 第3回スフィンゴテラピィ研究会
  • Place of Presentation: 鳥取
• [Presentation] スフィンゴシンキナーゼによる抗癌剤感受性の制御機構 (2009)
  • Author(s): 川原さと実、河野早紀、竹下未希、中村光浩、岡野幸雄、原明、村手隆、野澤義則、坂野喜子
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Book] 医薬品情報学 (2011)
  • Author(s): 栄田敏之、橋詰勉編集
  • Total Pages: 221
  • Publisher: 廣川書店
• [Book] 医薬品情報学 (2011)
  • Author(s): 柴崎正勝
  • Total Pages: 222
  • Publisher: 廣川書店
• [Book] 「LC-MS/MSの基本原理とは」(分担執筆)<実務担当者のアンケートを集めた>分析法バリデーションQ & A集 (2010)
  • Publisher: 情報機構
• [Book] 分析法バリデーションQ&A集 (2010)
  • Author(s): 中村光浩(分担執筆)
  • Total Pages: 209
  • Publisher: (株)情報機構