Mechanism of anti-pruritic action of histamine H4 receptor antagonist and its usefulness in the treatment of itching dermatitis.

• Project/Area Number: 24590723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Chiba University
• Principal Investigator: YAMAURA Katsunori 千葉大学, 薬学研究科(研究院), 准教授 (10543069)
• Research Collaborator: SUWA Eriko
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: H4受容体拮抗薬 / ステロイド長期塗布誘発掻痒 / プロスタグランジンD2 (PGD2) / ケラチノサイト / サブスタンスP (SP) / ヒスタミン / マウス / 正常ヒト角化細胞 (NHEK) / 掻痒 / デキサメタゾン (DEX) / H4受容体アンタゴニスト (H4RA) / 一酸化窒素 (NO) / dexamethasone / H4受容体アンタゴニスト / ロイコトリエンB4 (LTB4) / LTA4 hydrolase inhibitor / サブスタンスP急性掻痒 / 痒み

Outline of Final Research Achievements

Topical glucocorticoids are the first-line therapy for chronic dermatitis. We previously reported that long-term topical glucocorticoids exacerbated pruritus in chronic dermatitis model mice. In this study, we clarified that oral dose of histamine H4 receptor antagonist prevented the worsening of pruritus, and additionally suppressed the inflammation. These results indicated that H4 receptor antagonist would be useful for prevention of the exacerbation of pruritus induced by topical glucocorticoids in patients with chronic dermatitis.

Research Products

• [Journal Article] Increased expression of the histamine H4 receptor following differentiation and mediation of the H4 receptor on interleukin-8 mRNA expressio n in HaCaT keratinocytes (2014)
  • Author(s): Eriko Suwa, Katsunori Yamaura, Shiori Sato, Koichi Ueno
  • Journal Title: Experimental Dermatology Volume: 23 Issue: 2 Pages: 138-140
  • DOI: 10.1111/exd.12313
  • Peer Reviewed
• [Journal Article] Sex-related differences in SLIGRL-induced pruritus in mice. (2014)
  • Author(s): Yamaura K, Tomono A, Suwa E, Ueno K
  • Journal Title: Life Sciences Volume: 94 Issue: 1 Pages: 54-57
  • DOI: 10.1016/j.lfs.2013.10.036
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of the histamine H4 receptor in dermal and articular tissue. (2013)
  • Author(s): Yamaura K, Shigemori A, Suwa E, Ueno K
  • Journal Title: Life Sciences Volume: 92 Issue: 2 Pages: 108-113
  • DOI: 10.1016/j.lfs.2012.10.030
  • Peer Reviewed
• [Journal Article] Topical royal jelly alleviates symptoms of pruritus in a murine model of allergic contact dermatitis. (2013)
  • Author(s): Yamaura K, Tomono A, Suwa E, Ueno K.
  • Journal Title: Pharmacognosy Mag. Volume: 9 Issue: 33 Pages: 9-13
  • DOI: 10.4103/0973-1296.108127
  • Peer Reviewed
• [Journal Article] Degradation Index for Quality Evaluation of Commercial Dietary Supplements of Bilberry Extract (2013)
  • Author(s): Masao Yamamoto, Katsunori Yamaura, Makiko Ishiwatari, Maki Shimada, Sayaka Kado, Hiroko Seki, Norimoto Shimada, and Koichi Ueno
  • Journal Title: Journal of Food Science Volume: 78 Issue: 3 Pages: 477-483
  • DOI: 10.1111/1750-3841.12043
  • Peer Reviewed
• [Journal Article] Difficulty for consumers in choosing commercial bilberry supplements by relying only on product label information. (2013)
  • Author(s): Yamamoto M, Yamaura K (co-first author), Ishiwatari M, Ueno K.
  • Journal Title: Pharmacognosy Res. Volume: 5 Issue: 3 Pages: 212-215
  • DOI: 10.4103/0974-8490.112432
  • Peer Reviewed
• [Journal Article] Sex differences in stress reactivity of hippocampal BDNF in mice are associated with the female preponderance of decreased locomotor activity in response to restraint stress. (2013)
  • Author(s): Yamaura K, Bi Y, Ishiwatari M, Oishi N, Fukata H, Ueno K.
  • Journal Title: Zoolog Sci. Volume: 30 Issue: 12 Pages: 1019-1024
  • DOI: 10.2108/zsj.30.1019
  • NAID: 40019900455
  • Peer Reviewed
• [Journal Article] Repeated application of glucocorticoids exacerbate pruritus via inhibition of prostaglandin D₂ production of mast cells in a murine model of allergic contact dermatitis (2012)
  • Author(s): Yamaura K, Doi R, Suwa E, Ueno K.
  • Journal Title: The Journal of Toxicological Sciences Volume: 37 Issue: 6 Pages: 1127-1134
  • DOI: 10.2131/jts.37.1127
  • NAID: 130004447013
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Journal Article] Increased expression of the histamine H4 receptor subtype in hypertrophic differentiation of chondrogenic ATDC5 cells. (2012)
  • Author(s): Yamaura K, Akiyama S, Ueno K.
  • Journal Title: J Cell Biochem Volume: 113 Issue: 3 Pages: 1054-1060
  • DOI: 10.1002/jcb.23436
  • Peer Reviewed
• [Journal Article] Lower expression of histamine H4 receptor in synovial tissues from patients with rheumatoid arthritis compared to those with osteoarthritis. (2012)
  • Author(s): Yamaura K, Oda M, Suzuki M, Ueno K.
  • Journal Title: Rheumatology International Volume: 32 Issue: 10 Pages: 3309-3313
  • DOI: 10.1007/s00296-011-2069-6
  • Peer Reviewed
• [Journal Article] Anthocyanins, but not anthocyanidins, from bilberry (Vaccinium myrtillus L.) alleviate pruritus via inhibition of mast cells degranulation. (2012)
  • Author(s): Yamaura K, Ishiwatari M, Yamamoto M, Shimada M, Bi Y, Ueno K.
  • Journal Title: J Food Sci Volume: 77 Issue: 12
  • DOI: 10.1111/j.1750-3841.2012.02974.x
  • Peer Reviewed
• [Journal Article] Protective effects of natsumikan (Citrus natsudaidai) extract on acetaminophen-induced lethal hepatotoxicity in mice. (2012)
  • Author(s): Yamaura K, Nakayama N, Shimada M, Ueno K.
  • Journal Title: Pharmacognosy Res Volume: 4 Issue: 4 Pages: 234-236
  • DOI: 10.4103/0974-8490.102274
  • Peer Reviewed
• [Journal Article] Antidepressant-like effects of young green barley leaf (Hordeum vulgare L.) in the mouse forced swimming test. (2012)
  • Author(s): Yamaura K, Nakayama N, Shimada M, Bi Y, Fukata H, Ueno K.
  • Journal Title: Pharmacognosy Res Volume: 1 Issue: 1 Pages: 22-26
  • DOI: 10.4103/0974-8490.91030
  • Peer Reviewed
• [Presentation] 長期外用ステロイド誘発掻痒に対するPGD2 受容体DP1 アゴニストの有用性. (2015)
  • Author(s): 船越彩花, 山浦克典, 大石信雄, 小沼盛司, 武井美紗子, 神戸直智, 佐藤洋美, 樋坂章博
  • Organizer: 第135回日本薬学会年会
  • Place of Presentation: 神戸学院大学
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 長期ステロイド塗布が誘発する掻痒増悪とプロスタグランジンD2の関与. (2015)
  • Author(s): 船越彩花, 山浦克典, 大石信雄, 小沼盛司, 武井美紗子, 神戸直智, 佐藤洋美, 樋坂章博
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Investigation on Combination Therapy of Histamine H4 Receptor Antagonist and Topical Glucocorticoid Application for Treatment of Chronic Skin Diseases. (2015)
  • Author(s): Seiji Onuma, Katsunori Yamaura, Nobuo Oishi, Ayaka Funakoshi, Naotomo Kambe, Koichi Ueno, Hiromi Sato, Akihiro Hisaka
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 長期ステロイド外用療法に伴う痒みの誘発. (2015)
  • Author(s): 山浦克典
  • Organizer: 千葉アレルギークリニカルカンファレンス2015
  • Place of Presentation: オークラ千葉ホテル
  • Year and Date: 2015-01-21
  • Invited
• [Presentation] Evaluation of Pruritus in Psoriatic Mouse Model Induced by Imiquimod. (2014)
  • Author(s): 大石信雄, 山浦克典, 武井美紗子, 神戸直智, 佐藤洋美, 樋坂章博
  • Organizer: 第8回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 熊本大学薬学部
  • Year and Date: 2014-11-15 – 2014-11-16
• [Presentation] Topical glucocorticoid-induced pruritus. (2014)
  • Author(s): Katsunori Yamaura
  • Organizer: 24th International Symposium of Itch
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] Imiquimod誘発乾癬モデルマウスを用いた掻痒評価系の確立 (2014)
  • Author(s): 大石信雄, 武井美紗子, 山浦克典, 神戸直智, 佐藤洋美, 樋坂章博
  • Organizer: 第131回日本薬理学会関東部会
  • Place of Presentation: 横浜市立大学
  • Year and Date: 2014-10-11
• [Presentation] マウス掻痒評価系における掻破行動に及ぼす性差の影響. (2014)
  • Author(s): 山浦克典, 伴野綾奈、佐藤洋美、上野光一
  • Organizer: 第21回日本免疫毒性学会学術年会
  • Place of Presentation: 徳島文理大学薬学部
  • Year and Date: 2014-09-11 – 2014-09-12
• [Presentation] ヒスタミンH4受容体拮抗薬の長期外用ステロイド療法に伴う掻痒予防の有用性. (2014)
  • Author(s): 小沼盛司, 山浦克典, 大石信雄, 船越彩花, 佐藤洋美, 上野光一
  • Organizer: 第21回日本免疫毒性学会学術年会
  • Place of Presentation: 徳島文理大学薬学部
  • Year and Date: 2014-09-11 – 2014-09-12
• [Presentation] 長期外用ステロイド療法に伴う掻痒増悪とヒスタミンH4受容体拮抗薬の有用性. (2014)
  • Author(s): 小沼盛司, 山浦克典, 伴野綾奈, 大石信雄, 船越彩花, 諏訪映里子, 田中里歩, 佐藤史織, 佐藤洋美, 上野光一
  • Organizer: 第41回日本毒性学会学術年会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2014-07-02 – 2014-07-04
• [Presentation] 長期ステロイド外用療法に伴う掻痒性皮膚毒性.(ｼﾝﾎﾟｼﾞｳﾑ講演) (2014)
  • Author(s): 山浦克典
  • Organizer: 第41回日本毒性学会学術年会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2014-07-02 – 2014-07-04
• [Presentation] ステロイド誘発性掻痒モデルにおける皮膚内PGD2の役割. (2014)
  • Author(s): 船越彩花, 山浦克典, 大石信雄, 伴野綾奈, 土居亮介, 上野光一.
  • Organizer: 第134回日本薬学会年会.
  • Place of Presentation: 熊本
• [Presentation] ヒスタミンH4Rをターゲットとする新たな難治性掻痒治療に関する研究. (2013)
  • Author(s): 諏訪映里子, 山浦克典, 佐藤史織、上野光一.
  • Organizer: 第7回次世代を担う若手医療薬科学シンポジウム.
  • Place of Presentation: 仙台
• [Presentation] ステロイド誘発性掻痒におけるステロイド薬の相対的効力の影響. (2013)
  • Author(s): 船越彩花, 山浦克典, 大石信雄, 伴野綾奈, 土居亮介, 上野光一.
  • Organizer: 第129回日本薬理学会関東部会.
  • Place of Presentation: 東京
• [Presentation] ステロイド誘発掻痒におけるマウス掻破行動に対するステロイド外用薬の作用強度の影響. (2013)
  • Author(s): 山浦克典, 船越彩花, 大石信雄, 伴野綾奈, 土居亮介, 上野光一.
  • Organizer: 第20回日本免疫毒性学会学術大会.
  • Place of Presentation: 東京
• [Presentation] ヒスタミンH4Rをターゲットとした新たな難治性掻痒に関する研究. (2013)
  • Author(s): 佐藤史織, 山浦克典, 諏訪映里子, 上野光一.
  • Organizer: 第40回日本毒性学会学術年会.
  • Place of Presentation: 千葉
• [Presentation] ステロイド外用薬が掻痒に与える影響―デキサメタゾン、プレドニゾロン、およびベタメタゾンでの比較. (2013)
  • Author(s): 大石信雄, 山浦克典，土居亮介，伴野綾奈，船越彩花，上野光一.
  • Organizer: 第40回日本毒性学会学術年会.
  • Place of Presentation: 千葉
• [Presentation] マウス急性掻痒モデルにおける性差. (2013)
  • Author(s): 伴野綾奈, 山浦克典, 上野光一.
  • Organizer: 第40回日本毒性学会学術年会.
  • Place of Presentation: 千葉
• [Presentation] Expression of histamine H4 receptor in human skin and amelioration of experimental acute pruritus using H4 receptor antagonist. (2012)
  • Author(s): Yamaura K, Suwa E, Ueno K.
  • Organizer: European Congress of Immunology
  • Place of Presentation: Glasgow, UK
• [Presentation] Histamine H4 receptor mediates dermal inflammation and pruritus in a hapten induced long-term experimental model. (2012)
  • Author(s): Suwa E, Yamaura K, Ueno K.
  • Organizer: European Congress of Immunology
  • Place of Presentation: Glasgow, UK
• [Presentation] An in vivo and in vitro analysis of the mechanism of glucocorticoids-induced pruritus in chronic allergic contact dermatitis. (2012)
  • Author(s): Doi R, Yamaura K, Suwa E, Ueno K.
  • Organizer: 22nd Internatinal Symposium of Itch
  • Place of Presentation: Tokyo, Japan
• [Presentation] ステロイド外用剤のプロスタグランジンD2産生抑制を介する掻痒誘発作用に関する研究 (2012)
  • Author(s): 山浦克典, 土居 亮介, 諏訪 映里子, 上野 光一
  • Organizer: 第39回日本毒性学会学術年会
  • Place of Presentation: 仙台
• [Book] Anti-pruritic and anti-inflammatory herbal or natural products for treatment of skin disease. In: Natural Bioactive Molecules: Impacts & Prospects (Brahmachari G, ed.). (2013)
  • Author(s): Yamaura K, Ueno K
  • Total Pages: 516
  • Publisher: Alpha Science International (Oxford)
• [Book] Expression of the histamine H4 receptor in human tissue. In: Allergic Diseases - Highlights in the Clinic, Mechanisms and Treatment, (Raffi Tachdjian, ed.) (2012)
  • Author(s): Yamaura K, Suzuki M, Namiki T and Ueno K
  • Total Pages: 554
  • Publisher: InTech
• [Patent(Industrial Property Rights)] ＤＰ１アゴニストとステロイドとを含有する外用剤 (2014)
  • Inventor(s): 山浦克典、船越彩花
  • Industrial Property Rights Holder: 山浦克典、船越彩花
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-194053
  • Filing Date: 2014-09-24