Anthralin modulates the expression pattern of cytokeratins and antimicrobial peptides by psoriatic keratinocytes
| Autor: | Kamran Ghoreschi, Birgit Fehrenbacher, Julia Holstein, Iris Schäfer, Melanie Carevic, Eva Müller-Hermelink, Birgit Schittek, Jürgen Brück, Franziska C. Eberle, Martin Schaller |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Keratinocytes beta-Defensins Biopsy Antimicrobial peptides Fluorescent Antibody Technique Apoptosis Dermatology Biology Administration Cutaneous Biochemistry Interleukin 22 Tissue Culture Techniques 03 medical and health sciences In vivo Psoriasis Dithranol medicine Humans Molecular Biology Cells Cultured Cell Proliferation Skin Interleukin-6 Interleukins Keratin-16 Interleukin-17 Interleukin-8 Cell Differentiation Anthralin Keratin-10 medicine.disease 030104 developmental biology medicine.anatomical_structure Beta defensin Ki-67 Antigen Immunology Cancer research Keratin-5 Interleukin 17 Dermatologic Agents Keratinocyte medicine.drug |
| Zdroj: | Journal of dermatological science. 87(3) |
| ISSN: | 1873-569X |
| Popis: | Background Psoriasis is an inflammatory skin disease with aberrant keratinocyte proliferation, presumably as a result of immune cell activation. Th17 cytokines like IL-17A and IL-22 are critically implicated in epidermal thickening, altered keratinocyte differentiation and production of innate factors such as antimicrobial peptides. Psoriasis treatment options include modern targeted therapies using anti-cytokine antibodies and traditional non-targeted treatments like anthralin (dithranol). While the mode of action of anti-cytokine antibodies is defined, the effects of topical anthralin on psoriatic skin are not fully understood. Objective This study aims to unravel the direct effects of anthralin on keratinocyte proliferation, differentiation and production of psoriasis-associated factors. Methods We tested the effects of anthralin on cell proliferation, cytokeratin expression and changes in the expression of antimicrobial peptides using primary keratinocytes and 3D psoriasis tissue models with and without stimulation of the psoriasis-promoting cytokines IL-17A and IL-22. Moreover, we compared the findings derived from monolayer and multilayer cultures to data derived from lesional skin of patients with psoriasis before and under treatment with anthralin. Results Our study shows that anthralin directly induces cell apoptosis in vitro in monolayer cultures but not in 3D psoriasis tissue models treated with IL-17A and IL-22. Yet, keratinocyte proliferation as determined by Ki-67 staining is impaired by anthralin in vivo . In lesional skin but not in 3D psoriasis tissue models anthralin rapidly normalizes cytokeratin (CK)16 expression. Furthermore, anthralin directly inhibits DEFB4 expression in vitro and in vivo , while other antimicrobial peptides and cytokines studied like IL-6 and IL-8 are regulated differently in vitro and in vivo . Conclusions Our results show that anthralin directly regulates DEFB4A expression. However, its beneficial effects on psoriasis cannot be explained by direct effects on keratinocyte differentiation or cytokine expression. |
| Databáze: | OpenAIRE |
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