Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in Reconstructed and Ex Vivo Skin Models
| Autor: | Manon Roquet, Jean-Paul Chappuis, Béatrice Bertino, Estelle Soares, Carine Rosignoli, Séverine Thibaut de Ménonville, Chaussade, David Piwnica, Claire Defoin-Platel |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Calcitriol medicine.medical_treatment Human skin Dermatology Cathelicidin 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Ivermectin medicine Original Research Innate immunity Innate immune system business.industry KLK5 medicine.disease 030104 developmental biology Rosacea Immunology business Ex vivo medicine.drug |
| Zdroj: | Dermatology and Therapy |
| ISSN: | 2193-8210 |
| DOI: | 10.1007/s13555-017-0176-3 |
| Popis: | Introduction Numerous intrinsic and extrinsic factors have been associated with the pathophysiology of rosacea, including dysregulation of innate immunity. A high level of cathelicidin antimicrobial peptides (e.g., LL-37) has been shown in the facial skin of patients with rosacea. Excessive production of both LL-37 and KLK5, the serine protease responsible for its cleavage, has been suggested to play a role in the pathophysiology of rosacea. Ivermectin 10 mg/g cream, indicated for the treatment of inflammatory lesions of rosacea, is reported to have dual anti-parasitic and anti-inflammatory properties. However, the exact mechanism of action of ivermectin cream in the treatment of rosacea is unknown. Methods This study aimed to evaluate the effect of ivermectin on the expression of KLK5 and the subsequent effect on the maturation process of cathelicidins. Experimental studies were performed either on normal human epidermal keratinocytes (NHEK), reconstructed human epidermis (RHE) or on human skin ex vivo stimulated with calcitriol (1α,25-dihydroxyvitamin D3), which is known to induce KLK5 and LL-37 expression. Results The results show that ivermectin is able to inhibit KLK5 and CAMP gene expression and protein secretion in NHEK cells stimulated with calcitriol. Those results were confirmed in 3D models of the skin (RHE and skin ex vivo). The anti-inflammatory effects of ivermectin were associated with an inhibition of IL-8, IL-6 and MCP-1 (CCL2) secretion from NHEK cells. Conclusions These results suggest that ivermectin can prevent the inflammatory effects of rosacea triggered by abnormal LL-37 processing, through the inhibition of KLK5 gene expression in the epidermis. Funding: Nestlé Skin Health R&D. Electronic supplementary material The online version of this article (doi:10.1007/s13555-017-0176-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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