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2011 Fiscal Year Final Research Report

Control of itch by topical application of cholecystokinin and its use for novel therapy

Research Project

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Project/Area Number 22659208
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

TOKURA Yoshiki  浜松医科大学, 医学部, 教授 (00172156)

Co-Investigator(Kenkyū-buntansha) MORI Tomoko  産業医科大学, 医学部, 助教 (80399203)
Project Period (FY) 2010 – 2011
Keywordsコレシストキニン / かゆみ / 神経ペプチド / 肥満細胞 / 角化細胞 / 血管内皮細胞 / サブスタンスP / CCK2R
Research Abstract

Cholecystokinin(CCK) serves as a gastrointestinal hormone and also functions as a neuropeptide in central nervous system(CNS). CCK may be a downregulator in CNS as represented by its anti-opioid properties. The existence of CCK in peripheral nervous system has also been reported. We investigated the suppressive effects of various CCKs on the peripheral pruritus in mice. ICR mice were painted with CCK synthetic peptides on the clipped back and injected intradermally with substance P(SP) on the same site. The frequency of SP-induced scratch was reduced significantly by topical application of sulfated CCK8(CCK8S) and CCK7(CCK7S), but not by non-sulfated CCK8, CCK7 or CCK6. Dermal injection of CCK8S also depressed the scratch frequency, suggesting that dermal cells as well as epidermal keratinocytes are the targets of CCKs. By real-time PCR, mRNA for CCK2R, one of the two types of CCK receptors, was expressed highly in mouse fetal skin-derived mast cells(FSMCs) and moderately ICR mouse keratinocytes. CCK8S decreased in vitro compound 48/80-promoted degranulation of FSMCs with a transient elevation of the intracellular calcium concentration. These findings suggest that CCK exerts an anti-pruritic effect mainly via mast cells, and topical CCK may be clinically useful for pruritic skin disorders.

  • Research Products

    (37 results)

All 2011 2010 2009 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (9 results) Book (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Topical cholecystokinin depresses itch-as sociated scratching behavior in mice2011

    • Author(s)
      Fukamachi S, Mori T, Sakabe J-I, Shirai shi N, Kuroda E, Kobayashi M, Bito T, Kabashima K, Nakamura M, Tokura Y
    • Journal Title

      J I nvest Dermatol

      Volume: 131 Pages: 956-961

    • Peer Reviewed
  • [Journal Article] Modulation of semaphorin 3A expression by calcium concentration and histamine in human keratinocytes and fib roblasts2011

    • Author(s)
      Fukamachi S, Bito T, Shiraishi N, Koba yashi M, Kabashima K, Nakamura M, T okura Y
    • Journal Title

      J Dermatol Sci

      Volume: 62 Pages: 118-123

    • Peer Reviewed
  • [Journal Article] Efficacy of combined topical treatment of acne vul garis with adapalene and nadifloxacin : A randomized study2011

    • Author(s)
      Kobayashi M, Nakagawa T, Fukamachi K, Nakamura M, Tokura Y
    • Journal Title

      J Dermatol

      Volume: 38 Pages: 1163-1166

    • Peer Reviewed
  • [Journal Article] Downmodulatory effects of cetirizine and levocetirizine on cytokine/chemokine production and C D54 expression in keratinocytes2011

    • Author(s)
      Kobayashi M, Tokura Y
    • Journal Title

      J Derm atol

      Volume: 38 Pages: 717-719

    • Peer Reviewed
  • [Journal Article] Characterization of Peripheral Natural Killer Cells and their Reduction in Drug-induce d Hyper-sensitivity Syndrome2011

    • Author(s)
      Sugita K, Kabashima K, Tokura Y
    • Journal Title

      Acta Der m Venereol

      Volume: 92 Pages: 83-84

    • Peer Reviewed
  • [Journal Article] Increased expression of mRNAs for I L-4, IL-17, IL-22 and IL-31 in skin lesi ons of subacute and chronic forms of pr urigo2011

    • Author(s)
      Park K, Mori T, Nakamura M, Tokura Y
    • Journal Title

      Eur J Dermatol

      Volume: 21 Pages: 135-136

    • Peer Reviewed
  • [Journal Article] Inflammatory cytokine expression in the skin lesions of tumour necrosis factor receptor-associated periodic syndrome2011

    • Author(s)
      Ohmori S, Nakamura M, Hino R, Kobayashi M, Tokura Y
    • Journal Title

      Rheumatology

      Volume: 51 Pages: 196-199

    • Peer Reviewed
  • [Journal Article] High-Mobility Group Box 1 Protein(HMGB1) as a N ovel Diagnostic Tool for Toxic Epiderma l Necrolysis and Stevens-Johnson Syndro me2011

    • Author(s)
      Nakajima S, Watanabe H, Tohyama M, Sugita K, Iijima M, Hashimoto K, Tokur a Y, Nishimura Y, Doi H, Tanioka M, Miyachi Y, Kabashima K
    • Journal Title

      Arch Dermatol

      Volume: 147 Pages: 1110-1112

    • Peer Reviewed
  • [Journal Article] Epiletic seiz ures and cholinergic urticaria with gener alized hypohidrosis and anhidrosis2011

    • Author(s)
      Sawada Y, Bito T, Kabashia R, Sugita K, Nakamura M, Tokura Y
    • Journal Title

      Eur J Dermatol

      Volume: 21 Pages: 99-100

    • Peer Reviewed
  • [Journal Article] A c ase of cholinergic urticaria associated wit h acquired generalized hypohidrosis and reduced acetylcholine receptors : cause an d effect?2011

    • Author(s)
      Nakamizo S, Kurosawa M, Sawada Y, T okura Y, Miyachi Y, Kabashima K
    • Journal Title

      Clin Exp Dermatol

      Volume: 36 Pages: 559-560

    • Peer Reviewed
  • [Journal Article] Inducible Nitric Oxide Synthase Downmodulates Contact Hypersensitivity by Suppressing Dendritic Cell Migration and Survival2010

    • Author(s)
      Sugita K, Kabashima K, Yoshiki R, Iken ouchi-Sugita A, Tsutsui M, Nakamura J, Yanagihara N, Tokura Y
    • Journal Title

      J Inves t Dermatol

      Volume: 130 Pages: 464-471

    • Peer Reviewed
  • [Journal Article] Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis2010

    • Author(s)
      Mori T, Ishida K, Mukumoto S, Yamada Y, Imokawa G, Kabashima K, Kobayas hi M, Bito T, Nakamura M, Ogasawara K, Tokura Y
    • Journal Title

      Br J Dermatol

      Volume: 162 Pages: 83-90

    • Peer Reviewed
  • [Journal Article] Involvement of Wnt signaling in dermal fibroblasts2010

    • Author(s)
      Kabashima K, Sakabe J-I, Yoshiki R, Ta bata Y, Kohno K, Tokura Y
    • Journal Title

      Am J Pathol

      Volume: 176 Pages: 721-732

    • Peer Reviewed
  • [Journal Article] Flaky tail mouse denotes human atopic dermatitis in the steady state and by to pical application with Dermatophagoides pteronyssimus extract2010

    • Author(s)
      Moniaga CS, Egawa G, Kawasaki H, Ch ikuma M, Honda T, Tanizaki H, Nakaji ma S, Matsuoka H, Kubo A, Tokura Y, Miyachi Y, Amagai M, Kabashima K
    • Journal Title

      Am J Pathol

      Volume: 176 Pages: 2385-2393

    • Peer Reviewed
  • [Journal Article] The mandatory role of IL-10-producing and OX40L-expresssing mature Langerhans cells in local UVB-induced immunosuppression2010

    • Author(s)
      Yoshiki R, Kabashima K, Sakabe J-I, Su gita K, Bito T, Nakamura M, Malissen B, Tokura Y
    • Journal Title

      J Immunol

      Volume: 84 Pages: 5670-5677

    • Peer Reviewed
  • [Journal Article] Ultraviolet light induces Stat3 acti vation in human keratinocytes and fibrob lasts through reactive oxygen species and DNA damage2010

    • Author(s)
      Bito T, Sumita N, Masaki T, Shirakawa T, Ueda T, Yoshiki R, Tokura Y, Nishig ori C
    • Journal Title

      Exp Dermatol

      Volume: 19 Pages: 654-660

    • Peer Reviewed
  • [Journal Article] Activated regulatory Tcells are the major Tcell type emigrating from the skin during a cutaneous immune response in mice2010

    • Author(s)
      Tomura M, Honda T, Tanizaki H, Otsuk a A, Egawa G, Tokura Y, Waldmann H, Hori S, Cyster JG, Watanabe T, Miyach i Y, Kanagawa O, Kabashima K
    • Journal Title

      J Clin Invest

      Volume: 120 Pages: 883-893

    • Peer Reviewed
  • [Journal Article] Cholinergic urticaria : Studies on the muscarinic cholinergic receptor M3 in the anhidrotic and hypohidrotic skin2010

    • Author(s)
      Sawada Y, Nakamura M, Bito T, Fukam achi S, Kabashima R, Sugita K, Hino R, Tokura Y
    • Journal Title

      J Invest Dermatol

      Volume: 130 Pages: 2683-2686

    • Peer Reviewed
  • [Journal Article] FTY720 regulates bone marrow egress of eosinop hils and modulates late phase skin reacti on in mice2010

    • Author(s)
      Sugita K, Kabashima K, Sakabe J-I, Yos hiki R, Tanizaki H, Tokura Y
    • Journal Title

      Am J Pathol

      Volume: 177 Pages: 1881-1887

    • Peer Reviewed
  • [Journal Article] Extrinsic and intrinsic types o f atopic dermatitis2010

    • Author(s)
      Tokura Y
    • Journal Title

      J Dermatol Sci

      Volume: 58 Pages: 1-7

    • Peer Reviewed
  • [Journal Article] Rosa cea-like demodicosis mimicking cutaneou s lymphoma

    • Author(s)
      Kito Y, Hashizume H, Tokura Y
    • Journal Title

      Acta Derm Venereol

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] Haemodialysis-induced pseudoporphyria successfully treated with glutathione

    • Author(s)
      Kasuya A, Hashizume H, Tokura Y
    • Journal Title

      Eur J Dermatol

      Volume: (in press)

    • Peer Reviewed
  • [Presentation] Th17細胞と皮膚疾患2011

    • Author(s)
      戸倉新樹
    • Organizer
      第39回日本臨床免疫学会総会
    • Place of Presentation
      東京都
    • Year and Date
      20110915-17
  • [Presentation] Skin barrier impairment is het erogeneous in atopic dermatitis2011

    • Author(s)
      Tokura Y
    • Organizer
      The 36th Annual Meeting of the Japanese Socie ty for Investigative Dermatology
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2011-12-10
  • [Presentation] Atopic dermatitis and skin ba rrier in the extrinsic and intrinsic types2011

    • Author(s)
      Tokura Y
    • Organizer
      The 37^<th> Annual Meeting of the Taiwane se Dermatological Association
    • Place of Presentation
      Taipei, Taiwan.
    • Year and Date
      2011-11-26
  • [Presentation] 内因性アトピー性皮膚炎2011

    • Author(s)
      戸倉新樹
    • Organizer
      第62回日本皮膚科学会中部支部学術大会
    • Place of Presentation
      四日市
    • Year and Date
      2011-11-20
  • [Presentation] 外来性物質に対する皮膚アレルギー反応機構2011

    • Author(s)
      戸倉新樹
    • Organizer
      第61回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京都
    • Year and Date
      2011-11-11
  • [Presentation] Extrinsic and intrinsic types o f atopic dermatitis. Ancillary Meeting on Atopic Dermatitis2011

    • Author(s)
      Tokura Y
    • Organizer
      22^<nd> World Congress of Dermatology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-05-24
  • [Presentation] Recent concept on the role of cutaneous dendritic cells in UVB-induce d immunosuppression2011

    • Author(s)
      Tokura Y
    • Organizer
      22^<nd> World Congress of Dermatology 2011
    • Place of Presentation
      Seo ul, Korea
    • Year and Date
      2011-05-24
  • [Presentation] 外因性.内因性という分別はアトピー性皮膚炎に必要か2011

    • Author(s)
      戸倉新樹
    • Organizer
      第16回アトピー性皮膚炎治療研究会シンポジウム
    • Place of Presentation
      小倉市
    • Year and Date
      2011-02-05
  • [Presentation] Extrinsic and intrinsic types of atopic dermatitis2010

    • Author(s)
      Tokura Y
    • Organizer
      The 35^<th> Annual Mee ting of Japanese Society for Investigative Dermatology
    • Place of Presentation
      Wakayama Prefectural Cultural Hall, Wakayama
    • Year and Date
      2010-12-04
  • [Book] Hypersensitivity to mosquito bites and EBV2011

    • Author(s)
      Tokura Y
    • Total Pages
      423-428
    • Publisher
      MEDRANG
  • [Book] 皮膚科臨床アセット1.アトピー性皮膚炎2011

    • Author(s)
      戸倉新樹
    • Total Pages
      130-135
    • Publisher
      中山書店
  • [Book] 皮膚疾患最新の治療2011-20122011

    • Author(s)
      戸倉新樹
    • Total Pages
      117
    • Publisher
      南江堂
  • [Book] 皮膚科診療カラーアトラス大系2011

    • Author(s)
      戸倉新樹
    • Total Pages
      58, 86-88
    • Publisher
      講談社
  • [Book] 臨床医必携-全身とかゆみ2011

    • Author(s)
      戸倉新樹
    • Total Pages
      124-126
    • Publisher
      診断と治療社
  • [Patent(Industrial Property Rights)] 皮膚疾患治療薬2009

    • Inventor(s)
      戸倉新樹・深町晶子
    • Industrial Property Rights Holder
      産業医科大学・浜松医科大学
    • Industrial Property Number
      特許、2009-244528
    • Filing Date
      2009-10-23

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Published: 2013-07-31  

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