Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel
| Autor: | Richard L. Gallo, Alvin B. Coda, Tissa Hata, Julie C Harper, James Q Del Rosso, Jeremiah Miller, Faiza Shafiq, David Audish, Paul Kotol, Kenshi Yamasaki, Aimee M. Two |
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| Rok vydání: | 2013 |
| Předmět: |
Keratinocytes
Male Administration Topical medicine.medical_treatment Cathelicidin Cohort Studies Mice Reference Values Risk Factors Gene expression Dicarboxylic Acids Prospective Studies Cells Cultured Mice Inbred BALB C biology KLK5 Middle Aged Treatment Outcome Female Kallikreins medicine.drug Adult Azelaic acid Enzyme-Linked Immunosorbent Assay Dermatology Article Drug Administration Schedule Cathelicidins medicine Animals Humans Aged Serine protease Protease Dose-Response Relationship Drug business.industry Kallikrein medicine.disease Disease Models Animal stomatognathic diseases Rosacea Immunology biology.protein Serine Proteases business Gels Biomarkers Antimicrobial Cationic Peptides Follow-Up Studies |
| Zdroj: | Journal of the American Academy of Dermatology. 69:570-577 |
| ISSN: | 0190-9622 |
| DOI: | 10.1016/j.jaad.2013.05.019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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