2003 Fiscal Year Annual Research Report

皮膚樹状細胞における皮膚プリオン蛋白発現の制御機序の解析

Research Project

Project/Area Number	14570817
Research Institution	Fukushima Medical University School of Medicine
Principal Investigator	中村晃一郎福島県立医科大学, 医学部, 助教授 (60175502)
Keywords	ランゲルハンス細胞 / プリオン / インターロイキン1 / TNF-α
Research Abstract	プリオン病は変異型プリオン(PrP)蛋白が蓄積することによって生じる疾患であり、中枢神経の異常が認められる。本疾患の伝播経路には脾臓の樹状細胞(DC)がPrP伝播に関与していることが報告されており、さらに皮膚を介する経路として皮膚におけるDCの関与も推測されている。申請者はこれまで皮膚樹状細胞であるランゲルハンス細胞(LC)が正常プリオン蛋白を有すること、またPrP遺伝子欠損マウスでは皮膚LCの正常PrP発現が抑制されることを報告した。今年度はLCに対するサイトカインの影響について検討し、さらにFclgG受容体発現に対するPrP蛋白の影響についても検討した。この結果、(1)IL-1β、TNF-α(10ng/ml)はLCの接着分子CD40,CD80,CD86発現を有意に増加させた。(2)IL-1β、TNF-α(10ng/ml)刺激下に24,48時間培養したLCで、正常型PrP蛋白発現が有意に増加し、これらのサイトカインの刺激によってLCのPrPの発現が顕著に変化することが明らかとなった。(3)さらにリコンビナントPrP蛋白((1)μg/ml)で刺激した場合、24時間後にLCのCD40,CD80発現は有意に増加し、接着分子発現の増加を認めた。(4)PrP蛋白によるLCのFclgG受容体発現には変化を認めなかった。以上からPrP蛋白がLCの接着分子を介した抗原提示能に変化を与えることが明らかとなった。この結果はPrP伝伝播経路のなかでLCの機能変化が重要である可能性を示唆しており、PrPの機能を解析する上で重要であると考えられた。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Tsunemi Y, Nishibu A, Saeki H, Oyama N, Nakamura K, et al.: "Lack of Association between the Promoter Polymorphisms at Positions -308 and -238 of the Tumor Necrosis Factor Alpha Gene and Psoriasis vulgaris in Japanese Patients"Dermatology. 207(4). 371-374 (2003)
[Publications] Kagami S, Kakinuma T, Saeki H, Nakamura K, et al.: "Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis : serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis"Clin Exp Immunol. 134(2). 309-313 (2003)
[Publications] Tsunemi Y, Sekiya T, Saeki H, Nakamura K, et al.: "Lack of association of CCR3 single nucleotide polymorphism with atopic dermatitis in Japanese population"J Dermatol Sci. 33(2). 130-133 (2003)
[Publications] Xiao T, Fujita H, Saeki H, Torii H, Nakamura K, Asahina A, Tamaki K, et al.: "Thymus and activation-regulated chemokine (TARC/CCL17) produced by mouse epidermal Langerhans cells is upregulated by TNF-alpha and IL-4 and downregulated by IFN-gamma"Cytokine. 23(4-5). 126-132 (2003)
[Publications] Zheng X, Nakamura K, Tojo M, Akiba H, Y, et al.: "Ultraviolet A irradiation inhibits thymus and activation-regulated chemokine (TARC/CCL17) production by a human keratinocyte HaCaT cell line"Eur J Dermatol. 13(4). 348-353 (2003)
[Publications] Takahashi T, Nakamura K, et al.: "V alpha ; 24(+) natural killer T cells are markedly decreased in atopic dermatitis patients"Hum Immunol. 64(6). 586-592 (2003)
[Publications] Xiao T, Nakamura K, Tamaki K, et al.: "Both IL-4 and IL-13 inhibit the TNF-alpha and IFN-gamma enhanced MDC production in a human keratinocyte cell line, HaCaT cells"J Dermatol Sci. 31(2). 111-117 (2003)
[Publications] Kakinuma T, Asahina A, Nakamura K, Tamaki K, et al.: "Increased serum cutaneous T cell-attracting chemokine (CCL27) levels in patients with atopic dermatitis and psoriasis vulgaris"J Allergy Clin Immunol. 111(3). 592-597 (2003)
[Publications] Zheng X, Nakamura_K, Furukawa H, et al.: "Demonstration of TARC and CCR4 mRNA expression and distribution using in situ RT-PCR in the lesional skin of atopic dermatitis"J Dermatol. 30(1). 26-32 (2003)
[Publications] Kakinuma T, Wakugawa M, Nakamura K, Tamaki K, et al.: "High level of thymus and activation-regulated chemokine in blister fluid and sera of patients with bullous pemphigoid"Br J Dermatol. 148(2). 203-210 (2003)
[Publications] Kakinuma T, Sugaya M, Nakamura K, et al.: "Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides : serum TARC levels reflect the disease activity of mycosis fungoides"J Am Acad Dermatol. 48(1). 23-30 (2003)

2003 Fiscal Year Annual Research Report

皮膚樹状細胞における皮膚プリオン蛋白発現の制御機序の解析

Principal Investigator

中村 晃一郎 福島県立医科大学, 医学部, 助教授 (60175502)

Research Products

[Publications] Tsunemi Y, Nishibu A, Saeki H, Oyama N, Nakamura K, et al.: "Lack of Association between the Promoter Polymorphisms at Positions -308 and -238 of the Tumor Necrosis Factor Alpha Gene and Psoriasis vulgaris in Japanese Patients"Dermatology. 207(4). 371-374 (2003)

[Publications] Tsunemi Y, Sekiya T, Saeki H, Nakamura K, et al.: "Lack of association of CCR3 single nucleotide polymorphism with atopic dermatitis in Japanese population"J Dermatol Sci. 33(2). 130-133 (2003)

[Publications] Xiao T, Fujita H, Saeki H, Torii H, Nakamura K, Asahina A, Tamaki K, et al.: "Thymus and activation-regulated chemokine (TARC/CCL17) produced by mouse epidermal Langerhans cells is upregulated by TNF-alpha and IL-4 and downregulated by IFN-gamma"Cytokine. 23(4-5). 126-132 (2003)

[Publications] Zheng X, Nakamura K, Tojo M, Akiba H, Y, et al.: "Ultraviolet A irradiation inhibits thymus and activation-regulated chemokine (TARC/CCL17) production by a human keratinocyte HaCaT cell line"Eur J Dermatol. 13(4). 348-353 (2003)

[Publications] Takahashi T, Nakamura K, et al.: "V alpha ; 24(+) natural killer T cells are markedly decreased in atopic dermatitis patients"Hum Immunol. 64(6). 586-592 (2003)

[Publications] Xiao T, Nakamura K, Tamaki K, et al.: "Both IL-4 and IL-13 inhibit the TNF-alpha and IFN-gamma enhanced MDC production in a human keratinocyte cell line, HaCaT cells"J Dermatol Sci. 31(2). 111-117 (2003)

[Publications] Kakinuma T, Asahina A, Nakamura K, Tamaki K, et al.: "Increased serum cutaneous T cell-attracting chemokine (CCL27) levels in patients with atopic dermatitis and psoriasis vulgaris"J Allergy Clin Immunol. 111(3). 592-597 (2003)

[Publications] Zheng X, Nakamura_K, Furukawa H, et al.: "Demonstration of TARC and CCR4 mRNA expression and distribution using in situ RT-PCR in the lesional skin of atopic dermatitis"J Dermatol. 30(1). 26-32 (2003)

[Publications] Kakinuma T, Wakugawa M, Nakamura K, Tamaki K, et al.: "High level of thymus and activation-regulated chemokine in blister fluid and sera of patients with bullous pemphigoid"Br J Dermatol. 148(2). 203-210 (2003)

[Publications] Kakinuma T, Sugaya M, Nakamura K, et al.: "Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides : serum TARC levels reflect the disease activity of mycosis fungoides"J Am Acad Dermatol. 48(1). 23-30 (2003)

中村晃一郎福島県立医科大学, 医学部, 助教授 (60175502)