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Development of in vitro alternative examination for drug-induced photo-allergic reaction or drug-induced allergic reaction

Research Project

Project/Area Number 22590543
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionKobe University

Principal Investigator

BITO Toshinori  神戸大学, 医学部附属病院, 講師 (50324918)

Co-Investigator(Kenkyū-buntansha) TOKURA Yoshiki  浜松医科大学, 医学部, 教授 (00172156)
日野 亮介  産業医科大学, 医学部, 講師 (30446116)
Co-Investigator(Renkei-kenkyūsha) HINO Ryousuke  産業医科大学, 医学部, 講師 (30446116)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアレルギー / 光アレルギー / 表皮細胞 / 金属 / リンパ球刺激試験
Research Abstract

We investigated the concentration and exposure time of H_2O_2necessary for the development of skin damage in healthy volunteers with immunohistochemistry for signal transducer and activator of transcription3 (Stat3). The International Labour Office has warned that contact of concentrated hydrogen peroxide (H_2O_2) with skin or mucosa can cause severe inflammatory changes. When the skin is exposed to 35% H_2O_2, erythema, purpura, and even subcutaneous emphysema may occur,as documented in several case reports. It remains unknown how much concentration of H_2O_2and how long exposure to it evokes skin changes. Stat3 response to outer stress rescues the damaged cells from apoptosis, as Stat3 activation through oxidative stress has been observed in human lymphocytes. However, there has been no data on Stat3 andoxidative stress in human skin. Here we investigated the concentration and exposure time of H_2O_2necessary for the development of skin damage in healthy volunteers with immunohistoch … More emistry for Stat3. Our study also demonstrated that Stat3 activation is a good hallmark for H_2O_2damage. We have recently demonstrated that H_2O_2directly phosphorylates Stat3 protein without mediating membrane receptors or cytokines in human epidermal keratinocytes and fibroblasts. The observation seen in this study is consistent with those in vitrodata. Thus, Stat3 activation precedes the clinical and histological changes in the H_2O_2-exposed skin, and phosopho-Stat3 protein disappeared when the cells were seriously damaged as seen in 10 or 30 min-exposure to 30% H_2O_2. We published this data on the Journal of Dermatological Science. In addition, we have evaluated the allergenicity and photo-allergenicity of ketoprofen, which is known as a photo-sensitizing agent, by using THP-1 lymphocytes in vitro assay, and have demonstrated the partial usefulness for the evaluation of toxicity and allergenicity of the materials. The data were presented at 28thannual meeting of University of Occupational and EnvironmentalHealth. Less

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (20 results)

All 2012 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (4 results) Remarks (3 results)

  • [Journal Article] Impact of reactive oxygen species on keratinocyte signaling pathways2012

    • Author(s)
      Bito T, Nishigori C
    • Journal Title

      J Dermatol Sci

      Volume: 68 Pages: 3-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type2012

    • Author(s)
      Kabashima-Kubo R, Nakamura M, Sakabe J, Sugita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y
    • Journal Title

      J Dermatol Sci.

      Volume: 67 Pages: 37-43

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenesis of cholinergic urticaria in relation to sweating.2012

    • Author(s)
      Bito T, Sawada Y, Tokura Y.
    • Journal Title

      Allergol Int.

      Volume: 61 Pages: 539-544

    • NAID

      130004873059

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of reactive oxygen species on keratinocyte signaling pathways.2012

    • Author(s)
      Bito T, Nishigori C.
    • Journal Title

      J Dermatol Sci.

      Volume: 68 Pages: 3-8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type.2012

    • Author(s)
      Kabashima-Kubo R, Nakamura M, Sakabe J, Sugita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y.
    • Journal Title

      J Dermatol Sci.

      Volume: 67 Pages: 37-43

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of epidermal growth factor receptor and PI3K/Akt signaling suppresses cell proliferation and survival through regulation of Stat3 activation in human cutaneous squamous cell carcinoma2011

    • Author(s)
      Bito T, Sumita N, Ashida M, Budiyanto A, Ueda M, Ichihashi M, Tokura Y, Nishigori C
    • Journal Title

      J Skin Cancer

      Volume: 2011 Pages: 874571-874571

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epileptic seizures and cholinergic urticaria with generalized hypohidrosis or anhidrosis2011

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

      Eur J Dermatol

      Volume: 21 Pages: 99-100

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dysfunction of melanocytes in photoleukomelanoderma following photosensitivity caused by hydrochlorothiazide2011

    • Author(s)
      Masuoka E, Bito T, Shimizu H, Nishigori C.
    • Journal Title

      Photodermatol Photoimmunol Photomed

      Volume: 27 Pages: 328-30

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dysfunction of melanocytes in photoleukomelanoderma following photosensitivity caused by hydrochlorothiazide2011

    • Author(s)
      Masuoka E, Bito T, Shimizu H, Nishigori C
    • Journal Title

      Photodermatol Photoimmunol Photomed

      Volume: 27 Issue: 6 Pages: 328-330

    • DOI

      10.1111/j.1600-0781.2011.00614.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Primary cutaneous small cell carcinoma of the vulva arising from squamous cell carcinoma2011

    • Author(s)
      Matsumoto R, Bito T, Washio K, Ikeda T, Oka M, Manabe T, Nishigori C
    • Journal Title

      Br J Dermatol

      Volume: 165 Issue: 5 Pages: 1147-1148

    • DOI

      10.1111/j.1365-2133.2011.10451.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photochemical stability of lipoic acid and its impact on skin ageing2011

    • Author(s)
      Matsugo S, Bito T, Konishi T
    • Journal Title

      Free Radic Res

      Volume: 45 Pages: 918-924

    • NAID

      120003273419

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of toxicity and Stat3 activation induced by hydrogen peroxide exposure to the skin in healthy individuals2010

    • Author(s)
      Bito T, Izu K, Tokura Y
    • Journal Title

      J Dermatol Sci

      Volume: 58 Pages: 157-159

    • NAID

      10027400961

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of toxicity and Stat3 activation induced by hydrogen peroxide exposure to the skin in healthy individuals.2010

    • Author(s)
      Bito T, Izu K, Tokura Y
    • Journal Title

      J Dermatol Sci

      Volume: 58 Pages: 157-159

    • NAID

      10027400961

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒドロクロロチアジドによる光線過敏症型薬疹に合併した白斑黒皮症とその発症機序2011

    • Author(s)
      舛岡恵律子、清水秀樹、尾藤利憲、錦織千佳子
    • Organizer
      第62回日本皮膚科学会中部支部学術大会
    • Place of Presentation
      三重県四日市市
    • Year and Date
      2011-11-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒドロクロロチアジド配合剤による光線2010

    • Author(s)
      舛岡恵律子、田中えり子、小野竜輔、清水秀樹、尾藤利憲、岡昌宏、錦織千佳子
    • Organizer
      過敏型薬疹の 5 例第40回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
    • Place of Presentation
      広島
    • Year and Date
      2010-12-11
    • Related Report
      2012 Final Research Report
  • [Presentation] 産業化学物質及び薬剤のアレルギー性及び光アレルギー性 in vitro 評価2010

    • Author(s)
      尾藤利憲、日野亮介、森智子 、小林美和 、椛島健治、戸倉新樹
    • Organizer
      第28回産業医科大学学会
    • Place of Presentation
      北九州
    • Year and Date
      2010-10-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 産業化学物質及び薬剤のアレルギー性及び光アレルギー性in vitro評価2010

    • Author(s)
      尾藤利憲、日野亮介、森智子、小林美和、椛島健治、戸倉新樹
    • Organizer
      第28回産業医科大学学会
    • Place of Presentation
      産業医科大学(福岡県)(招待講演)
    • Year and Date
      2010-10-18
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://hifunavi.umin.jp/navitoha.html

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://hifunavi.umin.jp/navitoha.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://hifunavi.umin.jp/navitoha.html

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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