Ming-Wei Zhou1, Ri-Hua Jiang2, Ki-Duck Kim3, Jin-Hyup Lee3, Chang-Deok Kim3, Wei-Tian Yin4, Jeung-Hoon Lee5. 1. Department of Dermatology, The Third Hospital of Jilin University, Changchun, Jilin 130033, China; Department of Dermatology, School of Medicine, Chungnam National University, Daejeon 35015, Korea. 2. Department of Dermatology, The Third Hospital of Jilin University, Changchun, Jilin 130033, China. 3. Department of Dermatology, School of Medicine, Chungnam National University, Daejeon 35015, Korea. 4. Department of Orthopaedics, The Third Hospital of Jilin University, Changchun, Jirlin 130033, China. Electronic address: 109425381@qq.com. 5. Department of Dermatology, School of Medicine, Chungnam National University, Daejeon 35015, Korea; Skin Med Company, Daejeon 34028, Korea. Electronic address: jhoon@cnu.ac.kr.
Abstract
AIMS: Keratinocytes are the predominant cells in the epidermis, exerting their primary role of physical barrier through sophisticated differentiation process. In addition, keratinocytes contribute to the activation of innate immunity, providing the surveillant role against external pathogens. It has been known that chronic skin inflammatory disease such as psoriasis can be provoked by viral pathogens including double-stranded RNA. In this study, we demonstrated that rosmarinic acid (RA) has an inhibitory potential on inflammatory reaction induced by double-stranded RNA mimic poly(I:C) in epidermal keratinocytes. MAIN METHODS: We cultured human epidermal keratinocytes and induced inflammatory reaction by poly(I:C) treatment. The effect of RA on inflammatory reaction of keratinocytes was determined by RT-PCR and Western blot. KEY FINDINGS: RA significantly inhibited poly(I:C)-induced expression of inflammatory cytokines including IL-1β, IL-6, IL-8, CCL20, and TNF-α, and downregulated NF-κB signaling pathway in human keratinocytes. In addition, RA significantly inhibited poly(I:C)-induced inflammasome activation, in terms of secretion of active form of IL-1β and caspase-1. Furthermore, RA markedly inhibited poly(I:C)-induced NLRP3 and ASC expression. SIGNIFICANCE: These results indicate that RA can inhibit poly(I:C)-induced inflammatory reaction of keratinocytes, and suggest that it may be a potential candidate for the treatment of psoriasis.
AIMS: Keratinocytes are the predominant cells in the epidermis, exerting their primary role of physical barrier through sophisticated differentiation process. In addition, keratinocytes contribute to the activation of innate immunity, providing the surveillant role against external pathogens. It has been known that chronic skin inflammatory disease such as psoriasis can be provoked by viral pathogens including double-stranded RNA. In this study, we demonstrated that rosmarinic acid (RA) has an inhibitory potential on inflammatory reaction induced by double-stranded RNA mimic poly(I:C) in epidermal keratinocytes. MAIN METHODS: We cultured human epidermal keratinocytes and induced inflammatory reaction by poly(I:C) treatment. The effect of RA on inflammatory reaction of keratinocytes was determined by RT-PCR and Western blot. KEY FINDINGS:RA significantly inhibited poly(I:C)-induced expression of inflammatory cytokines including IL-1β, IL-6, IL-8, CCL20, and TNF-α, and downregulated NF-κB signaling pathway in human keratinocytes. In addition, RA significantly inhibited poly(I:C)-induced inflammasome activation, in terms of secretion of active form of IL-1β and caspase-1. Furthermore, RA markedly inhibited poly(I:C)-induced NLRP3 and ASC expression. SIGNIFICANCE: These results indicate that RA can inhibit poly(I:C)-induced inflammatory reaction of keratinocytes, and suggest that it may be a potential candidate for the treatment of psoriasis.
Authors: Joanna Sutkowska; Natalia Hupert; Katarzyna Gawron; Jakub W Strawa; Michał Tomczyk; Antonella Forlino; Anna Galicka Journal: Pharmaceutics Date: 2021-06-23 Impact factor: 6.321