Korean journal of dermatology (대한피부과학회지)

Korean Dermatological Association (대한피부과학회)
권호 표지

Clinical Improvement of Atopic Dermatitis by a Topical Cream Containing a Protease-Activated Receptor-2 (PAR-2) Inhibitor 'Pal-KTTKS Peptide'

Protease-Activated Receptor-2 (PAR-2) 억제제 'Pal-KTTKS 펩타이드' 탐색 및 이를 함유한 국소도포제에 의한 아토피피부염의 임상적 호전

  • Lee, Yoon-Hee (Department of Dermatology, Yonsei University Wonju College of Medicine) ;
  • Kim, Min-Jung (Department of Physiology, Yonsei University Wonju College of Medicine) ;
  • Kong, In-Duck (Institute of Basic Medical Science, Yonsei University Wonju College of Medicine) ;
  • Ryu, Jong-Sung (Research Institute of LG Household & Health Care Ltd.) ;
  • Jang, Min-Yeol (Research Institute of LG Household & Health Care Ltd.) ;
  • Lee, Cheon-Gu (Research Institute of LG Household & Health Care Ltd.) ;
  • Choi, Eung-Ho (Department of Dermatology, Yonsei University Wonju College of Medicine)
  • 이윤희 (연세대학교 원주의과대학 피부과학교실) ;
  • 김민정 (연세대학교 원주의과대학 생리학교실) ;
  • 공인덕 (연세대학교 원주의과대학 기초의학연구소) ;
  • 류종성 (LG생활건강 기술연구원) ;
  • 장민열 (LG생활건강 기술연구원) ;
  • 이천구 (LG생활건강 기술연구원) ;
  • 최응호 (연세대학교 원주의과대학 피부과학교실)
  • Received : 2010.08.12
  • Accepted : 2010.10.25
  • Published : 2010.11.30
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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.

Keywords

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