Bifonazole Exerts Anti-Inflammatory Effects in Human Three-Dimensional Skin Equivalents after UVB or Histamine Challenge
| العنوان: | Bifonazole Exerts Anti-Inflammatory Effects in Human Three-Dimensional Skin Equivalents after UVB or Histamine Challenge |
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| المؤلفون: | Katharina Fietkau, Jens M. Baron, Yvonne Marquardt, Sebastian Huth, Norbert-Heinz Becker, Laura Huth, Ruth Heise |
| المصدر: | Skin Pharmacology and Physiology. 32:337-343 |
| بيانات النشر: | S. Karger AG, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Keratinocytes, 0301 basic medicine, Receptors, Retinoic Acid, Ultraviolet Rays, Physiology, medicine.drug_class, CYP1B1, Bifonazole, Anti-Inflammatory Agents, Inflammation, Dermatology, Pharmacology, Anti-inflammatory, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, Cytochrome P-450 Enzyme System, Intermediate Filament Proteins, Downregulation and upregulation, medicine, Humans, Skin, Chemistry, Macrophages, Imidazoles, General Medicine, Fibroblasts, Intercellular Adhesion Molecule-1, Keratin 1, Coculture Techniques, 030104 developmental biology, Cytokines, medicine.symptom, Histamine, medicine.drug |
| الوصف: | Background: In addition to its role as a broad-spectrum imidazole antifungal drug, data from animal models as well as human clinical trials also demonstrated an anti-inflammatory efficacy of bifonazole (BFZ). In the histamine wheal test and after UV radiation, BFZ showed antiphlogistic effects that were comparable to those of hydrocortisone. However, the underlying molecular mechanisms of the anti-inflammatory properties of BFZ are poorly understood. Methods: Performing an in vitro study we used full-thickness three-dimensional (3D) skin models containing macrophages as mediators of inflammation. We conducted two sets of experiments. In a first set we exposed our models to UVB irradiation to provoke an inflammation. A second approach used the addition of histamine into the culture medium. In both approaches, models were treated topically with a BFZ-containing ointment or a placebo ointment for 24 h, and then the effects were examined histologically as well as with microarray and quantitative real-time PCR analyses. Results: Histological examination showed that the BFZ-containing ointment reconstituted UVB- and histamine-mediated disorders within the skin models. Performing gene expression profiling in models that were treated with the BFZ-containing ointment after UVB irradiation, we detected an upregulation of differentiation markers (fillagrin, loricrin, and keratin 1), antimicrobial peptides (DEFB103A), and members of the cytochrome P450 family (CYP1A1 and CYP1B1) as well as a downregulation of genes that are involved in immune response (CCL22, CXCL12, CCL7, IRF1, ICAM1, TLR3, and RARRES3) and matrix metalloproteinases (MMP12 and MMP7). Models that were treated with the BFZ-containing ointment after histamine application showed an upregulation of members of the cytochrome P450 family (CAP1A1, CYP1B1, and CYP24A1) and a downregulation of immune response-associated genes (CXCL6, CXCL12, CCL8, IL6, and IL32). Conclusion: We present the first in vitro study showing anti-inflammatory effects of BFZ in human 3D skin models. To our knowledge, this is the first time that these effects could be translated from human clinical trials into an in vitro test system, allowing a more detailed examination of molecular mechanisms that were regulated by BFZ. |
| تدمد: | 1660-5535 1660-5527 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da30fd71ce0397bc4e5486a456baa9b1Test https://doi.org/10.1159/000502213Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....da30fd71ce0397bc4e5486a456baa9b1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16605535 16605527 |
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