Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel

Alvin B. Coda, Tissa Hata, Jeremiah Miller, David Audish, Paul Kotol, Aimee Two, Faiza Shafiq, Kenshi Yamasaki, Julie C. Harper, James Q. Del Rosso, Richard L. Gallo

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

Background Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to play a role in the pathophysiology of rosacea. Objective We sought to evaluate the effects of azelaic acid (AzA) on these elements of the innate immune system. Methods Gene expression and protease activity were measured in laboratory models and patients with rosacea during a 16-week multicenter, prospective, open-label study of 15% AzA gel. Results AzA directly inhibited KLK5 in cultured keratinocytes and gene expression of KLK5, Toll-like receptor-2, and cathelicidin in mouse skin. Patients with rosacea showed reduction in cathelicidin and KLK5 messenger RNA after treatment with AzA gel. Subjects without rosacea had lower serine protease activity (SPA) than patients with rosacea. Distinct subsets of patients with rosacea who had high and low baseline SPA were identified, and patients with high baseline exhibited a statistically significant reduction of SPA with 15% AzA gel treatment. Limitations Study size was insufficient to predict clinical efficacy based on the innate immune response to AzA. Conclusions These results show that cathelicidin and KLK5 decrease in association with AZA exposure. Our observations suggest a new mechanism of action for AzA and that SPA may be a useful biomarker for disease activity.

Original languageEnglish
Pages (from-to)570-577
Number of pages8
JournalJournal of the American Academy of Dermatology
Volume69
Issue number4
DOIs
Publication statusPublished - 2013 Oct
Externally publishedYes

Keywords

  • LL-37 rosacea
  • antimicrobial peptides
  • azelaic acid
  • cathelicidin
  • kallikrein 5
  • serine protease

ASJC Scopus subject areas

  • Dermatology

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