Development of novel therapeutic strategies and elucidation of mechanisms regulating allergic inflammation based on circadian rhythms

• Project/Area Number: 23688040
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Clinical veterinary science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: OHMORI Keitaro 東京農工大学, (連合)農学研究科(研究院), 講師 (20466915)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000); Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2011: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
• Keywords: アレルギー / サーカディアンリズム / 動物モデル

Research Abstract

Although allergic diseases have increased dramatically in recent years, effective therapy has yet to be established. The purpose of this study was to elucidate the mechanisms regulating allergic inflammation based on circadian rhythms in order to alleviate clinical signs/symptoms of allergy constantly in line with the circadian rhythms of the body. By using a mouse model for human atopic dermatitis and dogs, time-of-day dependent variations of allergic inflammation were detected, and were shown to be controlled by glucocorticoid derived from the adrenal glands. These results suggested that administration of glucocorticoid drugs based on circadian rhythms might efficiently regulate allergic reactions.

Research Products

• [Journal Article] Circadian rhythms and the effect of glucocorticoids on expression of the clock gene period1 in canine peripheral blood mononuclear cells (2013)
  • Author(s): Ohmori K, Nishikawa S, Oku K, Oida K, Amagai Y, Kajiwara N, Jung K, Matsuda A, Tanaka A, Matsuda H
  • Journal Title: Vet. J. 2013 Volume: (in press) Issue: 3 Pages: 402-407
  • DOI: 10.1016/j.tvjl.2012.10.010
  • Peer Reviewed
• [Journal Article] Antagonistic Regulation by the Transcription Factors C/EBPαand MITF Specifies Basophil and Mast Cell Fates (2013)
  • Author(s): Qi X, Hong J, Chaves L, Zhuang Y, Chen Y, Wang D, Chabon J, Graham B, Ohmori K, Li Y, Huang H
  • Journal Title: Immunity Volume: 25;39(1) Issue: 1 Pages: 97-110
  • DOI: 10.1016/j.immuni.2013.06.012
  • Peer Reviewed
• [Journal Article] Stem cell factor contributes to tumorigenesis of mast cells via an autocrine/paracrine mechanism. (2013)
  • Author(s): Amagai Y, Tanaka A, Matsuda A, Jung K, Ohmori K, Matsuda H.
  • Journal Title: J. Leukoc. Biol. Volume: 93(2) Issue: 2 Pages: 245-250
  • DOI: 10.1189/jlb.0512245
  • Peer Reviewed
• [Journal Article] Daily intake of Jeju groundwater improves the skin condition of the model mouse for human atopic dermatitis. (2013)
  • Author(s): Tanaka A, Jung K, Matsuda A, Jang H, Kajiwara N, Amagai Y, Oida K, Ahn G, Ohmori K, Kang KG, Matsuda H
  • Journal Title: Journal of Dermatology Volume: 40 Issue: 3 Pages: 193-200
  • DOI: 10.1111/1346-8138.12055
  • Peer Reviewed
• [Journal Article] Supplementation of the fermented soy product ImmuBalanceTM effectively reduces itching behavior of atopic NC/Tnd mice (2012)
  • Author(s): Matsuda A, Tanaka A, Pan W, Okamoto N, Oida K, Kingyo N, Amagai Y, Xia Y, Jang H, Nishikawa S, Kajiwara N, Ahn G, Ohmori K, Matsuda H
  • Journal Title: J. Dermatol. Sci Volume: 67(2) Issue: 2 Pages: 130-139
  • DOI: 10.1016/j.jdermsci.2012.05.011
  • Peer Reviewed
• [Journal Article] Measurement for Canine IgE Using Canine Recombinant High Affinity IgE Receptor α Chain (FcεRIα) (2012)
  • Author(s): Tsukui T, Sakaguchi M, Kurata K, Maeda S, Ohmori K, Masuda K, Tsujimoto H, Iwabuchi S
  • Journal Title: Journal of Veterinary Medical Science Volume: 74 Issue: 7 Pages: 851-856
  • DOI: 10.1292/jvms.10-0520
  • NAID: 130001879766
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Measurement of canine IgE using canine recombinant high affinity IgE receptor a chain (FcεRIα) (2012)
  • Author(s): Tsukui T, Sakaguchi M, Kurata K, Maeda s, Ohmori K, Masuda K, Tsujimoto H, Iwabuchi S
  • Journal Title: J.Vet.Med.Sci. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Mast cells function as an alternative modulator of adipogenesis through 15-deoxy-delta-12, 14-prostaglandin J2 (2012)
  • Author(s): Tanaka A, Nomura Y Matsuda A, Ohmori K, Matsuda H
  • Journal Title: Am.J.Physiol. Volume: 301
  • Peer Reviewed
• [Journal Article] Glucocorticoid sensitivity depends on expression levels of glucocorticoid receptors in canine neoplastic mast cells (2011)
  • Author(s): Matsuda A, Tanaka A, Amagai Y, Ohmori K, Nishikawa S, Xia Y, Karasawa K, Okamoto N, Oida K, Jang H, Matsuda H.
  • Journal Title: Vet Immunol Immunopathol Volume: 144 Issue: 3-4 Pages: 321-328
  • DOI: 10.1016/j.vetimm.2011.08.013
  • Peer Reviewed
• [Journal Article] Mast cells function as an alternative modulator of adipogenesis through 15-deoxy-delta-12, 14-prostaglandin J2 (2011)
  • Author(s): Tanaka A, Nomura Y, Matsuda A, Ohmori K, Matsuda H.
  • Journal Title: Am J Physiol Cell Physiol Volume: 301 Issue: 6 Pages: 1360-1367
  • DOI: 10.1152/ajpcell.00514.2010
  • Peer Reviewed
• [Journal Article] Silencing of Int6 gene restores function of the ischemic hindlimb in a rat model for peripheral arterial disease (2011)
  • Author(s): Okamoto N, Tanaka A, Jung K, Karasawa K, Orito K, Matsuda A, Amagai Y, Oida K, Ohmori K, Matsuda H.
  • Journal Title: diovasc Res Volume: 92 Issue: 2 Pages: 209-217
  • DOI: 10.1093/cvr/cvr203
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptorγ-mediated suppression of dendritic cell function prevents the onset of atopic dermatitis in NC/Tnd mice (2011)
  • Author(s): Jung K, Tanaka A, Fujita H, Matsuda A, Oida K, Karasawa K, Okamoto N, Ohmori K, Jee Y, Shin T, Matsuda H.
  • Journal Title: J Allergy Clin Immunol Volume: 127 Issue: 2 Pages: 420-429
  • DOI: 10.1016/j.jaci.2010.10.043
  • Peer Reviewed
• [Journal Article] Retinal degeneration and ed1 mutation in NC/Tnd mice-a human atopic dermatitis model (2011)
  • Author(s): Karasawa K, Tanaka A, Jung K, Matsuda A, Okamoto N, Oida K, Ebihara N, Ohmori K, Matsuda H
  • Journal Title: Curr. Eye Res Volume: 36 Issue: 4 Pages: 350-357
  • DOI: 10.3109/02713683.2010.542268
  • Peer Reviewed
• [Journal Article] Patterns of aquaporin expression in the canine eye (2011)
  • Author(s): Karasawa K, Tanaka A, Jung K, Matsuda A, Okamoto N, Oida K, Ohmori K, Matsuda H
  • Journal Title: Vet. J Volume: 190 Issue: 2 Pages: 72-77
  • DOI: 10.1016/j.tvjl.2010.12.027
  • Peer Reviewed
• [Journal Article] CCAAT/enhancer-binding protein alpha /EBPalpha) is critical for interleukin-4 expression in response to FcepsilonRI receptor cross-linking (2011)
  • Author(s): Qi X, Nishida J, Chaves L, Ohmori K, Huang H
  • Journal Title: J. Biol. Chem Volume: 286 Issue: 18 Pages: 16063-16073
  • DOI: 10.1074/jbc.m110.213389
  • Peer Reviewed
• [Journal Article] Silencing of Int6 gene restores function of the ischemic hindlimb in a rat model for peripheral arterial disease (2011)
  • Author(s): Okamoto N, Tanaka A, Jung K, Karasawa K, Orito K, Matsuda A, Amagai Y, Oida K, Ohmori K, Matsuda H
  • Journal Title: Cardiovasc.Res. Volume: 92 Pages: 209-217
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptor gamma-mediated suppression of dendritic cell function prevents the onset of atopic dermatitis in NCA/Tnd mice (2011)
  • Author(s): Jung K, Tanaka A, Fujita H, Matsuda A, Oida K, Karasawa K, Okamoto N, Ohmori K, Jee Y, Shin T, Matsuda H
  • Journal Title: J.Allergy Clin.Immunol. Volume: 127 Pages: 420-429
  • Peer Reviewed
• [Journal Article] Retinal degeneration and edl mutation in NC/Tnd mice-a human atopic dermatitis model (2011)
  • Author(s): Karasawa K, Tanaka A, Jung K, Matsuda A, Okamoto N, Oida K, Ebihara N, Ohmon K, Matsuda H
  • Journal Title: Curr.Eye Res. Volume: 36 Pages: 350-357
  • Peer Reviewed
• [Journal Article] Patterns of aquaporin expression in the canine eye (2011)
  • Author(s): Karasawa K, Tanaka A, Jung K, Matsuda A, Okamoto N, Oida K, Ohmori K, Matsuda H
  • Journal Title: Vet.J. Volume: 190 Pages: 72-77
  • Peer Reviewed
• [Journal Article] CCAAT/enhancer-bindine protein alpha /EBPalpha)is critical for interleukin-4 expression in response to FcepsilonRI receptor cross-linking (2011)
  • Author(s): Qi X, Nishida J, Chaves L, Ohmori K, Huang H.
  • Journal Title: J.Biol.Chem. Volume: 286 Pages: 16063-16073
  • Peer Reviewed
• [Presentation] アトピー性皮膚炎自然発症モデルマウスの引っ掻き行動におけるサーカディアンリズム解析 (2013)
  • Author(s): 大森啓太郎
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大学(岐阜県)
  • Year and Date: 2013-09-21
• [Presentation] アトピー性皮膚炎自然発症モデルマウスの引っ掻き行動におけるサーカディアンリズム解析 (2013)
  • Author(s): 大森啓太郎
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜
• [Presentation] Role of FcRgamma in the development of pruritus in atopic dermatitis (2012)
  • Author(s): Ohmori K, Oku K, Matsuda A, Jung K, Tanaka A, Matsuda H
  • Organizer: 22nd International Symposium of Itch
  • Place of Presentation: Bell Salle Jimbocho (東京)
  • Year and Date: 2012-10-06
• [Presentation] イヌ末梢血単核球における時計遺伝子の概日リズム解析 (2012)
  • Author(s): 大森啓太郎、西川翔、奥啓輔、松田彬、Jung Kyungsook、田中あかね、松田浩珍
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(岩手県)
  • Year and Date: 2012-09-16
• [Presentation] Circadian regulation of scratching behavior in NC/Tnd mice, a mouse model for human atopic dermatitis (2011)
  • Author(s): Ohmori K, Tanaka A, Matsuda A, Matsuda H
  • Organizer: XXII World Allergy Congress
  • Place of Presentation: メキシコ
  • Year and Date: 2011-12-07
• [Presentation] アトピー性皮膚炎自然発症モデルマウス(NC/Tndマウス)の引っ掻き行動におけるサーカディアンリズム解析 (2011)
  • Author(s): 大森啓太郎、田中あかね、松田彬、松田浩珍
  • Organizer: Conference of BioSignal and Medicine 2011
  • Place of Presentation: 長野
  • Year and Date: 2011-06-24
• [Presentation] アトピー性皮膚炎自然発症モデルマウス(NC/Tndマウス)の引つ掻き行動におけるサーカディアンリズム解析 (2011)
  • Author(s): 大森啓太郎、田中あかね、松田彬、松田浩珍
  • Organizer: Conference of BioSignal and Medicine 2011
  • Place of Presentation: 長野
  • Year and Date: 2011-06-24
• [Presentation] Investigation of the correlation between itch and inflammation during the early and late phases of allergic reaction (2011)
  • Author(s): Okamoto N, Tanaka A, Matsuda A, Ohmori K, Matsuda H
  • Organizer: European Academy of Allergy and Clinical Immunology
  • Place of Presentation: トルコ
  • Year and Date: 2011-06-14
• [Presentation] Circadian scratching behavior in NC/NgaTnd mice, a mouse model for human atopic dermatitis (2011)
  • Author(s): Ohmori k, Tanaka A, Matsuda A, Matsuda H
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: 韓国
  • Year and Date: 2011-05-27
• [Presentation] Pain sensitivity in NC/Tnd mice with atopic dermatitis
  • Author(s): Akane Tanaka, Yen Xia, Akira Matsuda, Kyungsook Jung, Keitaro Ohmori, Hiroshi Matsuda
  • Organizer: 22nd International Symposium of Itch
  • Place of Presentation: Tokyo, Bell Salle Jimbocho
• [Presentation] Role of FcRgamma in the development of pruritus in atopic dermatitis
  • Author(s): Keitaro Ohmori, Keisuke Oku, Akira Matsuda, Kyungsook Jung, Akane Tanaka, Hiroshi Matsuda
  • Organizer: 22nd International Symposium of Itch
  • Place of Presentation: Tokyo, Bell Salle Jimbocho
• [Presentation] 海藻の一種であるカジメに含まれるdieckolの肥満細胞に対する効果
  • Author(s): Ahn Ginnae、田中あかね、松田彬、大森啓太郎、岡本典子、Jeon You-Jin、松田浩珍
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手県、岩手大学
• [Presentation] 金属石鹸がアトピー性皮膚炎自然発症モデルNC/Tndマウスの皮膚症状に及ぼす影響
  • Author(s): 松田彬、田中あかね、Jung Kyungsook、大森啓太郎、高井政貴、吉成佑治、松田浩珍
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手県、岩手大学
• [Presentation] イヌ末梢血単核球における時計遺伝子の概日リズム解析
  • Author(s): 大森啓太郎、西川翔、奥啓輔、松田彬、Jung Kyungsook、田中あかね、松田浩珍
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手県、岩手大学
• [Presentation] アトピー性皮膚炎に対する知覚神経刺激への反応性とTRPV1の関連性の検討
  • Author(s): 夏彦、田中あかね、松田彬、大森啓太郎、松田浩珍
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手県、岩手大学
• [Presentation] アトピー性皮膚炎モデルマウスにおける皮膚pHと皮膚バリア損傷の関連性
  • Author(s): Jang Hyosun、田中あかね、松田彬、大森啓太郎、松田浩珍
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手県、岩手大学