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Journal of the American Academy of Dermatology
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le vendredi 19 juillet 2013
Doi : 10.1016/j.jaad.2013.05.019
accepted : 18 May 2013
Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel
 

Alvin B. Coda, MD a, Tissa Hata, MD a, Jeremiah Miller, MD a, David Audish, BS a, Paul Kotol, BS a, Aimee Two, MD a, Faiza Shafiq, MBBS a, Kenshi Yamasaki, MD, PhD b, Julie C. Harper, MD c, James Q. Del Rosso, DO d, Richard L. Gallo, MD, PhD a,
a Division of Dermatology, Department of Medicine, University of California–San Diego, La Jolla, California 
b Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan 
c Dermatology and Skin Care Center of Birmingham, Birmingham, Alabama 
d Las Vegas Skin and Cancer Clinics, Henderson, Nevada 

Reprint requests: Richard L. Gallo, MD, PhD, Division of Dermatology, Department of Medicine, University of California–San Diego, 9500 Gilman Dr, #0869, San Diego, CA 92093.
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.

The full text of this article is available in PDF format.

Key words : antimicrobial peptides, azelaic acid, cathelicidin, kallikrein 5, LL-37, rosacea, serine protease

Abbreviations used : AzA, CEA, DMSO, IGA, KLK5, mRNA, SPA



 Supported in part by National Institutes of Health grant R01-AR052728 to Dr Gallo and an investigator-initiated grant from Bayer (Intendis) to Drs Gallo, Hata, Del Rosso, and Harper.
 Disclosure: Dr Del Rosso currently serves or has recently (within the last 2 years) served as a consultant, speaker, and/or researcher for Bayer Dermatology. Dr Coda, Dr Miller, Mr Audish, Mr Kotol, Dr Two, Dr Yamasaki, and Dr Shafiq have no conflicts of interest to declare.



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