Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to play a role in the pathophysiology of rosacea.
We sought to evaluate the effects of azelaic acid (AzA) on these elements of the innate immune system.
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.
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.
Study size was insufficient to predict clinical efficacy based on the innate immune response to AzA.
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.Le texte complet de cet article est disponible en PDF.
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.