Malassezia Yeasts Produce a Collection of Exceptionally Potent Activators of the Ah (Dioxin) Receptor Detected in Diseased Human Skin
| Autor: | K Stathopoulou, Periklis Pappas, George Gaitanis, Ioannis D. Bassukas, Marios Marselos, Maria Galanou, Eleni Melliou, Michael S. Denison, Alexios-Leandros Skaltsounis, Aristea Velegraki, Nikitia Mexia, Prokopios Magiatis, Christophoros Vlachos |
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| Rok vydání: | 2013 |
| Předmět: |
Cell Extracts
Keratinocytes Carcinoma Hepatocellular Indoles CYP1B1 Human skin Dermatology Biochemistry Article Microbiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Cytochrome P-450 CYP1A1 Dermatomycoses Homeostasis Humans RNA Messenger Molecular Biology Cell Line Transformed Skin 030304 developmental biology 0303 health sciences Malassezia integumentary system biology Liver Neoplasms Cell Biology Aryl hydrocarbon receptor biology.organism_classification Reverse transcriptase Yeast 3. Good health HaCaT Receptors Aryl Hydrocarbon chemistry 030220 oncology & carcinogenesis biology.protein Indirubin |
| Zdroj: | Journal of Investigative Dermatology. 133:2023-2030 |
| ISSN: | 0022-202X |
| Popis: | Malassezia yeasts are commensal microorganisms, which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia-associated diseases demonstrated 10- to 1,000-fold higher AhR-activating capacity than control skin extracts. Liquid chromatography-tandem mass spectrometry analysis of the patients' extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9 out of 12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture extracts and pure metabolites in HaCaT cells by reverse transcriptase real-time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1, and AhRR. Indirubin- and FICZ-activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared with the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development. |
| Databáze: | OpenAIRE |
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