Journal of the American Academy of Dermatology · 2013
Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel.
СтатьяМногоцентровое исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Coda Alvin B, Hata Tissa, Miller Jeremiah, Audish David, Kotol Paul, Two Aimee, Shafiq Faiza, Yamasaki Kenshi, Harper Julie C, Del Rosso James Q, Gallo Richard L
Аннотация
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.
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.
Предметные рубрики MeSH
Administration, TopicalAdultAgedAnimalsAntimicrobial Cationic PeptidesBiomarkersCells, CulturedCohort StudiesDicarboxylic AcidsDisease Models, AnimalDose-Response Relationship, DrugDrug Administration ScheduleEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesGelsHumansKallikreinsKeratinocytesMaleMiceMice, Inbred BALB CMiddle AgedProspective StudiesReference ValuesRisk FactorsRosaceaSerine ProteasesTreatment OutcomeCathelicidins