Regulation of chemokine production in inflammatory cutaneous disorders

2008 Fiscal Year Final Research Report

• Project/Area Number: 18591236
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Jichi Medical University (2007-2008); The University of Tokyo (2006)
• Principal Investigator: KOMINE Mayumi Jichi Medical University, 医学部・皮膚科学, 准教授 (00282632)
• Project Period (FY): 2006 – 2008
• Keywords: 炎症性皮膚疾患 / 乾癬 / 表皮細胞 / ケモカイン / 発現制御機構

Research Abstract

表皮細胞に発現するCTACK/CCL27、TARC/CCL17などのケモカインについて、トランスジェニックマウスを使用したin vivoの実験と、培養表皮細胞を用いたin vitroの実験から、炎症性皮膚疾患におけるケモカインの役割について検討した結果、CTACK/CCL27およびTARC/CCL17はアトピー性皮膚炎などの炎症性皮膚疾患において、接触アレルギー反応のなかでも特にTh2へ傾いた反応を増強する役割を持つことがわかった。また、表皮細胞から産生されるこれらのケモカインは治療薬である活性型ビタミンD3(カルシポトリオール、マキサカルシトール、天然型ビタミンD3)やステロイド剤(プロピオン酸クロベタゾール)により発現が制御されること、また活性型ビタミンD3の表皮ランゲルハンス細胞に対する作用を明らかにした。これらのことから乾癬やアトピー性皮膚炎に対するこれらの薬剤の効果の機序の一端が明らかとなった。また乾癬患者皮膚を用いた免疫組織学的検討により、乾癬局面周囲の、未だ明らかな皮膚病変を来たしていない部分においてもすでに早期の炎症性変化が生じており、この変化がリンパ球よりもむしろ樹状細胞により惹起されている可能性が示唆され、早期の炎症性変化をターゲットとした新たな治療の可能性が示唆された。

Research Products

• [Journal Article] Serum high molecular weight adiponectin levels are decreased in psoriasis patients. (2009)
  • Author(s): Shibata S, Saeki H, Tada Y, Karakawa M, Komine M, Tamaki K.
  • Journal Title: J Dermatol Sci.
  • Peer Reviewed
• [Journal Article] Erythroderma associated with leukocytosis in premalignant myeloproliferative disorder. (2009)
  • Author(s): Takatsuka Y, Komine M, Fujita E, Koike Y, Yamada T, Murata S, Ohtsuki M.
  • Journal Title: Int J Dermatol. 48(3) Pages: 324-6
  • Peer Reviewed
• [Journal Article] Pyoderma gangrenosum associated with Takayasu's arteritis without typical symptoms. (2009)
  • Author(s): Futaki K, Komine M, Hosoda S, Hirashima M, Yokokura H, Yamada T, Murata S, Matsuyama Y, Nagashima T, Nara H, Minota S, Ohtsuki M.
  • Journal Title: Eur J Dermatol. 19(3) Pages: 266-267
  • Peer Reviewed
• [Journal Article] Anti-cyclic citrullinated peptide antibodies and IL-23p19 in psoriatic arthritis. (2009)
  • Author(s): Shibata S, Tada Y, Komine M, Hattori N, Osame S, Kanda N, Watanabe S, Saeki H, Tamaki K.
  • Journal Title: J Dermatol Sci. 53(1) Pages: 34-9
  • Peer Reviewed
• [Journal Article] Serum 5-S-cysteinyldopa levels in patients with psoriasis undergoing narrowband ultraviolet B phototherapy. (2008)
  • Author(s): Kikuchi K, Wakamatsu K, Tada Y, Komine M, Ito S, Tamaki K.
  • Journal Title: Clin Exp Dermatol. 33(6) Pages: 750-3
  • Peer Reviewed
• [Journal Article] Juvenile pustular psoriasis associated with steroid withdrawal syndrome due to topical corticosteroid. (2008)
  • Author(s): Saeki H, Watanabe A, Tada Y, Kakinuma T, Komine M, Ihn H, Asahina A, Etoh T, Kitanaka S, Sato U, Kano H, Igarashi T, Tamaki K.
  • Journal Title: J Dermatol. 35(9) Pages: 601-3
  • Peer Reviewed
• [Journal Article] CCR4 and CCR10 are expressed on epidermal keratinocytes and are involved in cutaneous immune reaction. (2008)
  • Author(s): Fujimoto S, Uratsuji H, Saeki H, Kagami S, Tsunemi Y, Komine M, Tamaki K.
  • Journal Title: Cytokine. 44(1) Pages: 172-8
  • Peer Reviewed
• [Journal Article] Six novel mutations of the ADAR1 gene in patients with dyschromatosis symmetrica hereditaria: histological observation and comparison of genotypes and clinical phenotypes. (2008)
  • Author(s): Kondo T, Suzuki T, Mitsuhashi Y, Ito S, Kono M, Komine M, Akita H, Tomita Y.
  • Journal Title: J Dermatol. 35(7) Pages: 395-406
  • Peer Reviewed
• [Journal Article] Proliferating tricholemmal cystic carcinoma: a case containing differentiated and dedifferentiated parts. (2008)
  • Author(s): Masui Y, Komine M, Kadono T, Ishiura N, Maekawa T, Ihn H, Kikuchi K, Tamaki K.
  • Journal Title: J Cutan Pathol. 35 Suppl 1 Pages: 55-8
  • Peer Reviewed
• [Journal Article] CCL27-transgenic mice show enhanced contact hypersensitivity to Th2, but not Th1 stimuli. (2008)
  • Author(s): Kagami S, Saeki H, Tsunemi Y, Nakamura K, Kuwano Y, Komine M, Nakayama T, Yoshie O, Tamaki K.
  • Journal Title: Eur J Immunol. 38(3) Pages: 647-57
  • Peer Reviewed
• [Journal Article] A case of milia en plaque successfully treated with oral etretinate. (2007)
  • Author(s): Ishiura N, Komine M, Kadono T, Kikuchi K, Tamaki K.
  • Journal Title: Br J Dermatol. 157(6) Pages: 1287-9
  • Peer Reviewed
• [Journal Article] The involvement of Gab1 and PI 3-kinase in beta1 integrin signaling in keratinocytes. (2007)
  • Author(s): Kuwano Y, Fujimoto M, Watanabe R, Ishiura N, Nakashima H, Komine M, Hamazaki TS, Tamaki K, Okochi H.
  • Journal Title: Biochem Biophys Res Commun. 361(1) Pages: 224-9
  • Peer Reviewed
• [Journal Article] ERK inhibitor PD98059 promotes the phenotypic and functional maturation of murine resident Langerhans cells. (2007)
  • Author(s): Fujita H, Asahina A, Komine M, Tamaki K.
  • Journal Title: J Dermatol. 34(6) Pages: 403-6
  • Peer Reviewed
• [Journal Article] The direct action of 1alpha,25(OH)2-vitamin D3 on purified mouse Langerhans cells. (2007)
  • Author(s): Fujita H, Asahina A, Komine M, Tamaki K.
  • Journal Title: Cell Immunol. 245(2) Pages: 70-9
  • Peer Reviewed
• [Journal Article] Early inflammatory changes in the "perilesional skin" of psoriatic plaques: is there interaction between dendritic cells and keratinocytes? (2007)
  • Author(s): Komine M, Karakawa M, Takekoshi T, Sakurai N, Minatani Y, Mitsui H, Tada Y, Saeki H, Asahina A, Tamaki K.
  • Journal Title: J Invest Dermatol. 127(8) Pages: 1915-22
  • Peer Reviewed
• [Journal Article] Psoriasis vulgaris associated with superior vena cava syndrome due to lung cancer metastasis. (2007)
  • Author(s): Saeki H, Hosono S, Tsunemi Y, Sasaki K, Kadono T, Ihn H, Komine M, Asahina A, Kikuchi K, Tamaki K.
  • Journal Title: J Dermatol. 34(5) Pages: 356-9
  • Peer Reviewed
• [Journal Article] Serum uric acid levels in patients with vitiligo receiving narrowband ultraviolet B phototherapy. (2007)
  • Author(s): Kikuchi K, Komine M, Takekoshi T, Tamaki K.
  • Journal Title: Clin Exp Dermatol. 32(1) Pages: 107-8
  • Peer Reviewed
• [Journal Article] Sezary syndrome treated with narrowband ultraviolet B: time-course measurement of serum levels of CCL17/CCL27. (2007)
  • Author(s): Masui Y, Sugaya M, Kagami S, Fujita H, Yano S, Nagao M, Komine M, Saeki H, Ihn H, Kikuchi K, Tamaki K.
  • Journal Title: Clin Exp Dermatol. 32(1) Pages: 57-9
  • Peer Reviewed
• [Journal Article] Novel mutation (Asp158Val) in H1 domain of keratin 5 gene in a Japanese patient with Kobner-type epidermolysis bullosa simplex. (2006)
  • Author(s): Saeki H, Nakamura K, Tsunemi Y, Komine M, Tamaki K.
  • Journal Title: J Dermatol. 33(10) Pages: 692-5
  • Peer Reviewed
• [Journal Article] Treatment of HIV-associated eosinophilic pustular folliculitis with narrow-band UVB. (2006)
  • Author(s): Kuwano Y, Watanabe R, Fujimoto M, Komine M, Asahina A, Tsukada N, Tamaki K.
  • Journal Title: Int J Dermatol. 45(10) Pages: 1265-7
  • Peer Reviewed
• [Journal Article] A case of epidermolysis bullosa simplex with a newly found missense mutation and polymorphism in the highly conserved helix termination motif among type I keratins, which was previously reported as a pathogenic missense mutation. (2006)
  • Author(s): Hattori N, Komine M, Kaneko T, Shimazu K, Tsunemi Y, Koizumi M, Goto J, Hashimoto T.
  • Journal Title: Br J Dermatol. 155(5) Pages: 1062-3
  • Peer Reviewed
• [Journal Article] A novel keratin 9 gene mutation (Met156Arg) in a Japanese patient with epidermolytic palmoplantar keratoderma. (2006)
  • Author(s): Shimazu K, Tsunemi Y, Hattori N, Saeki H, Komine M, Adachi M, Tamaki K.
  • Journal Title: Int J Dermatol. 45(9) Pages: 1128-30
  • Peer Reviewed
• [Journal Article] Necrolytic migratory erythema without glucagonoma in a patient with short bowel syndrome. (2006)
  • Author(s): Nakashima H, Komine M, Sasaki K, Mitsui H, Fujimoto M, Ihn H, Asahina A, Kikuchi K, Tamaki K.
  • Journal Title: J Dermatol. 33(8) Pages: 557-62
  • Peer Reviewed
• [Journal Article] Treatment of psoriasis vulgaris with narrow-band UVB and topical Maxacalcitol. (2006)
  • Author(s): Takekoshi T, Asahina A, Komine M, Tamaki K.
  • Journal Title: Acta Derm Venereol. 86(4) Pages: 375-6
  • Peer Reviewed
• [Journal Article] CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuli. (2006)
  • Author(s): Tsunemi Y, Saeki H, Nakamura K, Nagakubo D, Nakayama T, Yoshie O, Kagami S, Shimazu K, Kadono T, Sugaya M, Komine M, Matsushima K, Tamaki K.
  • Journal Title: Eur J Immunol. 36(8) Pages: 2116-27
  • Peer Reviewed
• [Journal Article] Interleukin 12 production by monocytes from patients with psoriasis and its inhibition by ciclosporin A. (2006)
  • Author(s): Tada Y, Asahina A, Takekoshi T, Kishimoto E, Mitsui H, Saeki H, Komine M, Tamaki K.
  • Journal Title: Br J Dermatol. 154(6) Pages: 1180-3
  • Peer Reviewed
• [Journal Article] Activation of Akt by mechanical stretching in human epidermal keratinocytes. (2006)
  • Author(s): Yano S, Komine M, Fujimoto M, Okochi H, Tamaki K.
  • Journal Title: Exp Dermatol. 15(5) Pages: 356-61
  • Peer Reviewed
• [Presentation] Herpes gestationis in association with a complete hydatidiform mole (2008)
  • Author(s): Yuka Takatsuka、Mayumi Komine、et al.
  • Organizer: Japan-China Dermatology meeting
  • Place of Presentation: 杭州
  • Year and Date: 20081031-1103
• [Presentation] Existence of numerous CD1a- and RANKL-positive dendritic cells in the papillary dermis of psoriatic plaques. (2008)
  • Author(s): 小宮根真弓他
  • Organizer: International Investigative Dermatology
  • Place of Presentation: 京都
  • Year and Date: 20080514-17
• [Presentation] バイオロジックスと乾癬の病態理論の深化 (2008)
  • Author(s): 小宮根真弓
  • Organizer: 第 回乾癬学会ランチョンセミナー
  • Place of Presentation: 旭川
  • Year and Date: 2008-09-06
• [Presentation] 乾癬の病態:表皮側から (2008)
  • Author(s): 小宮根真弓
  • Organizer: 第 回乾癬学会シンポジウム
  • Place of Presentation: 旭川
  • Year and Date: 2008-09-05
• [Presentation] 抗菌剤の新しい作用 (2008)
  • Author(s): 小宮根真弓
  • Organizer: 107回日本皮膚科学会総会 イブニングセミナー
  • Place of Presentation: 京都
  • Year and Date: 2008-04-01
• [Presentation] アトピー性皮膚炎における表皮細胞の役割 (2008)
  • Author(s): 小宮根真弓
  • Organizer: 日本薬理学会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-19
• [Presentation] Early inflammatory in the "peri-lesional skin" of psoriatic plaques: Is there interaction between dendritic cells and keratinocytes? (2007)
  • Author(s): Mayumi Komine, Masaru Karakawa, Tomonori Takekoshi, Naoki sakurai, Yosaku Minatani, Hiroshi Mitsui, Yayoi Tada, Hidehisa Saeki, Akihiko Asahina, Kunihiko Tamaki
  • Organizer: the 10^<th> International Langerhans cell meeting
  • Place of Presentation: Bern, Switzerland
  • Year and Date: 20070902-04
• [Presentation] Early inflammatory in the "peri-lesional skin" of psoriatic plaques: Is there interaction between dendritic cells and keratinocytes? (2007)
  • Author(s): Mayumi Komine, Masaru Karakawa, Tomonori Takekoshi, Naoki sakurai, Yosaku Minatani, Hiroshi Mitsui, Yayoi Tada, Hidehisa Saeki, Akihiko Asahina, Kunihiko Tamaki
  • Organizer: the 63th Annual meeting of Society for Investigative Dermatology
  • Place of Presentation: Los Angeles, USA
  • Year and Date: 20070509-12
• [Presentation] The effects of mechanical stretch on normal human epidermal keratinocytes. (2007)
  • Author(s): Mayumi Komine, Yasushi Hanakawa, Hitoshi Okochi, Koji Sayama, Koji Hashimoto, Miroslav Blumenberg, Kunihiko Tamaki
  • Organizer: 第32 回 日本研究皮膚科学会
  • Place of Presentation: 東京(横浜)
  • Year and Date: 20070418-20
• [Presentation] 膿疱性乾癬皮疹部における樹状細胞と表皮細胞からのiNOS産生 (2007)
  • Author(s): 小宮根真弓、大槻マミ太郎、唐川大、竹腰知紀、柴田彩、多田弥生、佐伯秀久、玉置邦彦
  • Organizer: 第22 回日本乾癬学会
  • Place of Presentation: 三重(伊勢志摩)
  • Year and Date: 2007-09-07
• [Presentation] 水疱型先天性魚鱗癬様紅皮症のケラチン1変異による表皮細胞への影響、稀少難治性皮膚疾患に関する調査研究班 (2007)
  • Author(s): 小宮根真弓、花川 靖、橋本公二、大河内仁志、玉置邦彦
  • Organizer: 平成19年度第1回班会議
  • Place of Presentation: 東京
  • Year and Date: 2007-08-03
• [Presentation] ケラチノサイトの生物学 (2007)
  • Author(s): 小宮根真弓
  • Organizer: 第106回日本皮膚科学会総会教育講演
  • Place of Presentation: 東京(横浜)
  • Year and Date: 2007-04-22
• [Presentation] 抗菌剤の特性を生かす (2007)
  • Author(s): 小宮根真弓
  • Organizer: 第106回日本皮膚科学会総会モーニングセミナー
  • Place of Presentation: 東京(横浜)
  • Year and Date: 2007-04-22
• [Presentation] 生物学的製剤 (2007)
  • Author(s): 小宮根真弓
  • Organizer: 第106回日本皮膚科学会総会ランチョンセミナー
  • Place of Presentation: 東京(横浜)
  • Year and Date: 2007-04-20
• [Presentation] Immunohistochemical Study of NB-UVB-treated Skin of Psoriasis Patients (2006)
  • Author(s): Komine M, Deng D, Takekoshi T, Sakurai N, Minatani M, Saeki H, Asahina A, Tamaki K
  • Organizer: 第10回日本・中国合同皮膚科学会
  • Place of Presentation: 成都、中国
  • Year and Date: 2006-09-01
• [Presentation] 尋常性乾癬局面および膿疱性乾癬病変部における樹状細胞についての免疫組織学的検討 (2006)
  • Author(s): 小宮根真弓、竹腰知紀、桜井直樹、南谷洋策、佐伯秀久、朝比奈昭彦、玉置邦彦
  • Organizer: 第21回日本乾癬学会
  • Year and Date: 2006-09-01
• [Presentation] 表皮細胞における変異ケラチンK1の作用 (2006)
  • Author(s): 小宮根真弓、花川 靖、常深祐一郎、佐々木苗胤、大河内仁志、橋本公二、玉置邦彦
  • Organizer: 第21回角化症研究会
  • Year and Date: 2006-08-01
• [Presentation] Immunohistochemical characterization of the marginal lesion of psoriatic plaques (2006)
  • Author(s): Komine M, Takekoshi T, Sakurai N, Minatani M, Saeki H, Asahina A, Tamaki K.
  • Organizer: 第31回日本研究皮膚科学会
  • Year and Date: 2006-06-01
• [Presentation] Mechanical stretch induces extracellular matrix proteins, adhesion molecules, and actin-related cytoskeleton proteins, by regulating Rho, cdc42 and Rac family gene expression in normal human keratinocytes. (2006)
  • Author(s): Mayumi Komine, Shoichiro Yano, Hitoshi Okochi, Miroslav Blumenberg, Kunihiko Tamaki
  • Organizer: 第67回米国研究皮膚科学会
  • Place of Presentation: フィラデルフィア、アメリカ合衆国
  • Year and Date: 2006-05-01
• [Book] インターフェロンの使い方は?現場の疑問に答える皮膚病治療薬Q&A (2008)
  • Author(s): 小宮根真弓(宮地良樹、大谷道輝 編)
  • Total Pages: 311-313
  • Publisher: 中外医学社、東京
• [Book] 毛孔性苔癬(2008今日の治療指針) (2008)
  • Author(s): 小宮根真弓(総編集 山口徹、北原光夫、福井告次矢)
  • Total Pages: 887-888
  • Publisher: 医学書院、東京
• [Book] ジベルばら色ひこう疹 看護のための最新医学講座第二版第19巻皮膚科疾患 (2007)
  • Author(s): 小宮根真弓(中川秀己編)
  • Total Pages: 125-127
  • Publisher: 中山書店 東京
• [Book] 毛孔性紅色ひこう疹 看護のための最新医学講座第二版第19巻皮膚科疾患 (2007)
  • Author(s): 小宮根真弓(中川秀己編)
  • Total Pages: 123-125
  • Publisher: 中山書店 東京
• [Book] マクロライドはかゆみに効くか、WHAT'S NEW IN皮膚科学2006-2007 (2006)
  • Author(s): 小宮根真弓(宮地良樹編)
  • Total Pages: 137-138
  • Publisher: メディカルレビュー社
• [Book] かゆみに奏功する可能性のある既存薬、かゆみ最前線 (2006)
  • Author(s): 小宮根真弓(宮地良樹、生駒晃彦編)
  • Total Pages: 134-137
  • Publisher: メディカルレビュー社
• [Book] ここまでわかった乾癬の病態(WHAT'S NEW IN 皮膚科学2008-2009)
  • Author(s): 小宮根真弓(宮地良樹 編)
  • Publisher: メディカルレビュー社、 東京
• [Patent(Industrial Property Rights)] 白斑治療外用薬 (2008)
  • Inventor(s): 玉置邦彦、菊池かな子、小宮根真弓、藤本盛輝
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 特許出願
  • Filing Date: 2008