B-Cell Maturation Antigen (BCMA) Activation Exerts Specific Proinflammatory Effects in Normal Human Keratinocytes and Is Preferentially Expressed in Inflammatory Skin Pathologies
| Autor: | Andreas Tsapis, Elias Castanas, Valérie Dessirier, Marilena Kampa, Sanaa Sabour-Alaoui, Efstathios N. Stathopoulos, Maria Venihaki, George Notas, Vassilia-Ismini Alexaki, Vasiliki Pelekanou |
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| Rok vydání: | 2012 |
| Předmět: |
Keratinocytes
medicine.medical_specialty Cell type Transmembrane Activator and CAML Interactor Protein Tumor Necrosis Factor Ligand Superfamily Member 13 Dermatitis Human skin Biology Proinflammatory cytokine Endocrinology Internal medicine B-Cell Activating Factor medicine Humans B-Cell Maturation Antigen Receptor B-cell activating factor integumentary system Interleukin-6 NF-kappa B Granulocyte-Macrophage Colony-Stimulating Factor HaCaT medicine.anatomical_structure Gene Expression Regulation Epidermis Keratinocyte |
| Zdroj: | Endocrinology. 153:739-749 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2011-1504 |
| Popis: | TNFα is known to be expressed in human skin, regulating immune-related responses. Here we report that human normal skin keratinocytes express the members of the TNF superfamily members A proliferation-inducing ligand (APRIL; TNFSF13), B cell-activating factor (BAFF; TNFSF13B), and their receptors, B cell maturation antigen (BCMA; TNFRSF17) and transmembrane activator, calcium-modulator, and cyclophilin ligand interactor (TACI; TNFRSF13B), in a distinct spatial pattern. Our data show a differential expression of these molecules within epidermal layers and skin appendages, whereas the BAFF-specific receptor BAFFR (TNFRSF13C) is absent. Importantly, APRIL and BCMA but not BAFF or TACI are up-regulated in inflammatory skin lesions of psoriasis and squamous cell carcinomas. To explore the functional significance of this system in the skin, we assayed these receptors and ligands in cultured primary keratinocytes and HaCaT cells. We show that both cell types express BAFF, APRIL, BCMA, and TACI. Furthermore, APRIL and/or BAFF trigger nuclear factor-κB activation and IL-6 and granulocyte macrophage colony-stimulating factor (GM-CSF) expression through functional BCMA receptors, an activation inhibited by anti-BCMA short hairpin RNA. However, BAFF and/or APRIL do not induce IL-8 or TNFα production. Our data advance BCMA as an inflammation-related TNFSFR member in keratinocytes, of potential importance in the management of inflammatory skin conditions. |
| Databáze: | OpenAIRE |
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