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色素性乾皮症における免疫の異常

Research Project

Project/Area Number 08877134
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionKyoto University

Principal Investigator

錦織 千佳子  京都大学, 医学研究科, 助手 (50198454)

Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords色素性乾皮症 / (6-4)光産物 / ピリミジンダイマー / IL-10 / サイトカイン / 紫外線 / T4エンドヌクレアーゼ / TNF-α
Research Abstract

色素性乾皮症(XP)は紫外線によってDNAに生じた傷を修復する酵素を欠損するために、日光露光部に皮膚癌を生じる高発癌性遺伝疾患であるが、DNA修復酵素が転写の機能も担っているという概念が発見されたので、DNA修復異常疾患、とくに、XPにおける免疫系の異常を研究することが、本研究の目的である。それに先立ち、XP患者で修復することが出来ない紫外線によるDNA傷害であるビリミジンダイマーおよび(6-4)光産物のサイトカイン産生に及ぼす影響を調べた。マウス表皮細胞に太陽光近似の紫外線(波長のピークは305nmを200J/m2を照射後12時間後からIL-10の発現が見られ始め、24時間後の細胞が強く染色された。しかし、UV照射直後ビリミジンダイマーを特異的に修復する酵素T4Endonucleas Vを1時間処理あるいは、(6-4)光産物を特異的に修復する酵素である(6-4)光回復酵素を処理後光回復光を照射後、通常の培養液に戻して23時間後の細胞ではUV照射のみの群と比べてIL-10の染色性は明らかに減少した。チミンダイマーに特異的なモノクローナル抗体(TDM2)並びに(6-4)光産物に対するモノクローナル抗体(64M2)を用いてダイマー並びに(6-4)光産物の検出を行ったところUVB200J/m2照射後、T4N5リボゾームあるいは(6-4)光回復酵素に引き続き光回復光を処理することによってTDM2、64M2に対する染色性は明らかに減少した。以上のことにより紫外線によって生じるDNAの傷であるビリミジンダイマー、(6-4)光産物が抑制性のサイトカインであるIL-10の分泌を促進することが示唆された。さらに、XPA群のモデルマウスにUVB5kJ/m^2照射24時間後のIL-10の発現を抗マウスIL-10特異的モノクローナル抗体を用いて検出したところ、XPマウスでは正常マウスに比べてIL-10の発現が強く、XPAマウスでは接触過敏症反応が低下していることを支持するデータである。これらのことよりDNAの傷を修復できないことが、免疫の制御にも深く関わることが示唆ざれた。

Report

(3 results)
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Takashi Yagi: "Complete restoration of normal DNA repair characteristics in Group F xeroderma pigmentosum cells by over-expression of fransfected XPF cDNA" Carcinogenesis. 19. 55-60 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumura Y: "Mutations of P16/P15 Tumor Suppressor Genes and Replication Error Contribure Independently to the Pathogenesis of Sporadic Malignant Melanoma" Archive Dermatol Res. 290. 175-180 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumura Y: "Chatacterization of Molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms" Hum Mol Genet. 7. 969-974 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Chikako Nishigori: "Hind III liposomes suppress delayed-type hypersensitivity responses in vivo and production of epidermal IL-10 in vitro." J Immunol. 161. 2684-2691 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishigori C: "The effect of UV induced DNA damage on cytokine expression derived from keratiocytes." Photomedicine and Photobiology. 20. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 錦織千佳子: "遺伝子修復機能の異常 「図説分子病態学」" 中外医学社, 8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morita K: "Werner's syndrome-chromosomal analysis of cultured fibroblasts and mitogen-stimulated lymphocytes" Brit.J.Dermal.136. 620-623 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Chikako Nishigori: "Clinical characteristics and gene alterations in XPF gene in Japanese patients with xeroderma pigmentosum Group F" Photomedicine and Photobiology. 19. 43-44 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takashi Yagi: "Complete restration of normal DNA repair characteristics in Group F xeroderma pigmentosum cells by over-expression of transfected XPF cDNA" Carcinogenesis. 19. 55-60 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsumura Y: "Mutations of P16/P15 Tumor Suppressor Genes and Replication Error Contribute Independently to the Pathogenesis of Sporadic Malignant Melanonu" Arch.Dermatol.Res. (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsumura Y: "Chatacterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mind Symptoms" Hum.Mol Genet. (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Miho Matsui: "Proceedings for the 10th Japan-korea joint meeting of Dermatology." The oxidative Stress and the arsenic-induced Bowen's Disease, 4 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasuhiro Matsumura,Chikako Nishigori,Takashi Yagi: "Characterization of P53 gene mutations in pasal cell carcinomas:comparison between sun-exposed areas and less-exposed skin areas." Int.J.Cancer. 65. 778-780 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sato M,Nishigori C,Yagi T,Takebe H: "Aberrant splicing and truncated protein expression due to a hewly identified XPA gene mutations" Mutat Res. 362. 199-208 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Chikako Nishigori,Daniel B.Yarosh,cherrie Donawn,Margaret.L.Kripke: "The Immune System in UV carcinogenesis.J Invest Dermatol:Symposium Proceedings" Skin Cancer. 1. 143-146 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] O′Connor A,Nishigori C Yarosh D.B et al: "DNA donble strand breaks in epidermal cells canse immune suppression in vivo and production in vitro." J.Immunol.157. 271-278 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Chikako Nishigori,Daniel B.Yarosh Stephan E.Ullrich,et al: "DNA damage triggers IL-10 Cytokine production in UV-irradiated keratinocytes" Proc.Natl.Acad.Sci.U.S.A. 93. 10354-10359 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yukari Hattori,Chikako Nishigori Tomoyuki Tanaka,et al: "8-Hydroxy-Z deoxyguanosine is increased in epidermal cells Ofhairless mice after chronic UVB exposure" J Invest Dermatol. 107. 733-737 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morita K,Nishigori C,Sasaki M.S,Matsuyoshi N: "Brit.J.Dermatol" Werner′s syndrome-chromonomal analysis of cultured fibroblasts and mitogen-stimulated lymp Ocytes(in press),

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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