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      Protease-Activated Receptor-2 (PAR-2) 억제제 Pal-KTTKS 펩타이드 탐색 및 이를 함유한 국소도포제에 의한 아토피피부염의 임상적 호전 = Clinical Improvement of Atopic Dermatitis by a Topical Cream Containing a Protease-Activated Receptor-2 (PAR-2) Inhibitor Pal-KTTKS PeptideProtease-Activated Receptor-2 (PAR-2) 억제제 Pal-KTTKS 펩타이드 탐색 및 이를 함유한 국소도포제에 의한 아토피피부염의 임상적 호전

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      https://www.riss.kr/link?id=A82426205

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      다국어 초록 (Multilingual Abstract)

      Background: Serine protease promotes desquamatation of the stratum corneum and this is controlled by serine protease inhibitors (SPI). After disruption of the skin barrier, signals for barrier recovery are started with the activation of cytokines and a migration of calcium ions. On the other hand, the protease-activated receptor-2 (PAR-2) pathway is initiated as a negative signal. As the pH of the stratum corneum become neutral, activated serine protease and PAR-2 inhibit the secretion of lamellar bodies and the formation of the lamellar structure. Objective: We wanted to screen noble synthetic peptides and identify the efficacy of a selected peptide, Palmitic acid-Lysine Threonine Threonine Lysine Serine (Pal-KTTKS), on PAR-2 in vitro and in vivo, and a clinical study was performed. Methods: In vitro: Changes of the intracellular calcium ion concentration were measured in cultured HaCaT cells by fluorescence imaging according to treatment with sample peptides and trypsin. In vivo animal study: The efficacy of 2% Pal-KTTKS cream as a selected noble peptide was evaluated in an oxazolone-induced atopic dermatitis animal model. Clinical study: A total of twenty three atopic dermatitis patients applied 2.5% Pal-KTTKS peptide-containing cream on the one side of their extremities and pseudo-ceramide containing moisturizer on the other side of the extremities as a control twice a day for 4 weeks. Clinical improvement was evaluated by the Eczema Area Severity Index (EASI) score, a subject questionnaire and comparison of photographs. Results: Suppression of the intracellular calcium concentration via PAR-2 inhibition was noted in the Pal-KTTKS peptide treated cultured HaCaT cells. In the oxazolone-induced atopic dermatitis hairless mice model, 2% Pal-KTTKS peptide containing lotion was more effective than vehicle lotion only. In the atopic dermatitis patients, the sites treated with 2.5% Pal-KTTKS peptide-containing cream showed better improvement for the EASI score, the subject questionnaire and the clinical photographs as compared to that of the control sites. There were no remarkable side effects related to the treatment. Conclusion: A PAR-2 inhibitor-containing topical agent would be an effective and safe modality for treating atopic dermatitis. (Korean J Dermatol 2010;48(11):966∼974)
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      Background: Serine protease promotes desquamatation of the stratum corneum and this is controlled by serine protease inhibitors (SPI). After disruption of the skin barrier, signals for barrier recovery are started with the activation of cytokines and ...

      Background: Serine protease promotes desquamatation of the stratum corneum and this is controlled by serine protease inhibitors (SPI). After disruption of the skin barrier, signals for barrier recovery are started with the activation of cytokines and a migration of calcium ions. On the other hand, the protease-activated receptor-2 (PAR-2) pathway is initiated as a negative signal. As the pH of the stratum corneum become neutral, activated serine protease and PAR-2 inhibit the secretion of lamellar bodies and the formation of the lamellar structure. Objective: We wanted to screen noble synthetic peptides and identify the efficacy of a selected peptide, Palmitic acid-Lysine Threonine Threonine Lysine Serine (Pal-KTTKS), on PAR-2 in vitro and in vivo, and a clinical study was performed. Methods: In vitro: Changes of the intracellular calcium ion concentration were measured in cultured HaCaT cells by fluorescence imaging according to treatment with sample peptides and trypsin. In vivo animal study: The efficacy of 2% Pal-KTTKS cream as a selected noble peptide was evaluated in an oxazolone-induced atopic dermatitis animal model. Clinical study: A total of twenty three atopic dermatitis patients applied 2.5% Pal-KTTKS peptide-containing cream on the one side of their extremities and pseudo-ceramide containing moisturizer on the other side of the extremities as a control twice a day for 4 weeks. Clinical improvement was evaluated by the Eczema Area Severity Index (EASI) score, a subject questionnaire and comparison of photographs. Results: Suppression of the intracellular calcium concentration via PAR-2 inhibition was noted in the Pal-KTTKS peptide treated cultured HaCaT cells. In the oxazolone-induced atopic dermatitis hairless mice model, 2% Pal-KTTKS peptide containing lotion was more effective than vehicle lotion only. In the atopic dermatitis patients, the sites treated with 2.5% Pal-KTTKS peptide-containing cream showed better improvement for the EASI score, the subject questionnaire and the clinical photographs as compared to that of the control sites. There were no remarkable side effects related to the treatment. Conclusion: A PAR-2 inhibitor-containing topical agent would be an effective and safe modality for treating atopic dermatitis. (Korean J Dermatol 2010;48(11):966∼974)

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      참고문헌 (Reference)

      1 Denda M, "Trans-4-(aminomethyl)-cyclohexane carboxylic acid(t-AMCHA),an anti-fibrinolytic agent,accelerate barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans" 109 : 84-90, 1997

      2 Nystedt S, "The proteinaseactivated receptor 2 is induced by inflammatory mediators in human endothelial cells:comparison with the thrombin receptor" 271 : 14910-14915, 1996

      3 Sharlow E, "The protease-activated receptor-2 upregulates keratinocyte phagocytosis" 113 : 3093-3101, 2000

      4 Hachem JP, "Serine protease-induced alterations in permeability barrier homeostasis are mediated by protease-activated receptor-2" 124 : A58-, 2005

      5 Hachem JP, "Serine protease signaling of epidermal permeability barrier homeostasis" 126 : 2074-2086, 2006

      6 Holzhausen M, "Roles of protease- activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis" 100 (100): 177-180, 2005

      7 Rattenholl A, "Role of proteinase-activated receptors in cutaneous biology and disease" 59 : 408-416, 2003

      8 Nakamura T, "Reduction of skin barrier function by proteolytic activity of a recombinant house dust mite major allergen Der f 1" 126 : 2719-2723, 2006

      9 Steinhoff M, "Proteinase-activated receptor-2 mediates itch:a novel pathway for pruritus in human skin" 23 : 6176-6180, 2003

      10 Vergnolle N, "Protease-activated receptor-2 and hyperalgesia:a novel pain pathway" 7 : 821-826, 2001

      1 Denda M, "Trans-4-(aminomethyl)-cyclohexane carboxylic acid(t-AMCHA),an anti-fibrinolytic agent,accelerate barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans" 109 : 84-90, 1997

      2 Nystedt S, "The proteinaseactivated receptor 2 is induced by inflammatory mediators in human endothelial cells:comparison with the thrombin receptor" 271 : 14910-14915, 1996

      3 Sharlow E, "The protease-activated receptor-2 upregulates keratinocyte phagocytosis" 113 : 3093-3101, 2000

      4 Hachem JP, "Serine protease-induced alterations in permeability barrier homeostasis are mediated by protease-activated receptor-2" 124 : A58-, 2005

      5 Hachem JP, "Serine protease signaling of epidermal permeability barrier homeostasis" 126 : 2074-2086, 2006

      6 Holzhausen M, "Roles of protease- activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis" 100 (100): 177-180, 2005

      7 Rattenholl A, "Role of proteinase-activated receptors in cutaneous biology and disease" 59 : 408-416, 2003

      8 Nakamura T, "Reduction of skin barrier function by proteolytic activity of a recombinant house dust mite major allergen Der f 1" 126 : 2719-2723, 2006

      9 Steinhoff M, "Proteinase-activated receptor-2 mediates itch:a novel pathway for pruritus in human skin" 23 : 6176-6180, 2003

      10 Vergnolle N, "Protease-activated receptor-2 and hyperalgesia:a novel pain pathway" 7 : 821-826, 2001

      11 Boukamp P, "Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line" 106 : 761-771, 1988

      12 Cork MJ, "New perspectives on epidermal barrier dysfunction in atopic dermatitis:gene-environment interactions" 118 : 3-21, 2006

      13 Vu TKH, "Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation" 64 : 1057-1068, 1991

      14 Jeong SK, "Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery" 128 : 1930-1939, 2008

      15 Wahlgren CF, "Itch and atopic dermatitis:an overview" 26 : 770-779, 1999

      16 Santulli RJ, "Evidence for the presence of a protease-activated receptor distinct from the thrombin receptor in human keratinocytes" 92 : 9151-9155, 1995

      17 Akdis CA, "Diagnosis and treatment of atopic dermatitis in children and adults:European Academy of Allergology and Clinical Immunology American Academy of Allergy,Asthma and Immunology PRACTALL Consensus Report" 118 : 152-169, 2006

      18 D’Andrea MR, "Characterization of protease-activated receptor-2 immunoreactivity in normal human tissues" 46 : 157-164, 1998

      19 Man MQ, "Characterization of a hapten-induced,murine model with multiple features of atopic dermatitis:structural,immunologic,and biochemical changes following single versus multiple oxazolone challenges" 128 : 79-86, 2008

      20 Kim KH, "Atopic dermatitis, In: KDA textbook editing board. Dermatology. 5th ed" Ryo Moon Gak 170-172, 2008

      21 Hanifin JM, "Atopic dermatitis" 6 : 1-13, 1982

      22 Stefansson K, "Activation of proteinase-activated receptor-2 by human kallikrein related peptidase" 128 : 18-25, 2008

      23 Grynkiewicz G, "A new generation of Ca2+ indicators with greatly improved fluorescence properties" 260 : 3440-3450, 1985

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2010-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2008-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2006-06-29 학술지명변경 외국어명 : 미등록 -> Korean Journal of Dermatology KCI등재
      2006-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2003-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2002-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2000-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      학술지 인용정보

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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.11 0.11 0.13
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.13 0.14 0.254 0.01
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