Propranolol Is an Effective Topical and Systemic Treatment Option for Experimental Epidermolysis Bullosa Acquisita
| Autor: | Kazuko Matsumoto, Frank Petersen, Saeedeh Ghorbanalipoor, Pia Stüssel, Kathrin Kalies, Wendelien Veldkamp, Veronika Hartmann, Yask Gupta, Katharina Schulze Dieckhoff, Katja Bieber, Malin Krause, Gestur Vidarsson, Remco Visser, Sven Künzel, Georg Kaiser, Ralf Ludwig |
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| Přispěvatelé: | Landsteiner Laboratory, AII - Inflammatory diseases |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Epidermolysis bullosa acquisita Neutrophils Adrenergic beta-Antagonists Primary Cell Culture Administration Oral Dermatology Propranolol Pharmacology Epidermolysis Bullosa Acquisita Administration Cutaneous Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Immune system medicine Animals Humans RNA-Seq Receptor Molecular Biology Cells Cultured Skin business.industry Chemotaxis Cell Biology Gene signature medicine.disease Immune complex Healthy Volunteers Receptors Adrenergic Chemotaxis Leukocyte Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Tumor necrosis factor alpha business Transcriptome medicine.drug Signal Transduction |
| Zdroj: | Journal of investigative dermatology, 140(12), 2408-2420. Nature Publishing Group |
| ISSN: | 1523-1747 0022-202X |
| Popis: | Propranolol is an ADRB2 blocker that regulates heart muscle contractions, smooth muscle relaxation, and glycogenolysis. In addition, an increasing number of applications in dermatology have been described, most prominently, the use as a first-line treatment for infantile hemangiomas. We here show that propranolol enhances IL-8-induced neutrophil chemotaxis and reduces the release of ROS after immune complex stimulation. To obtain further molecular insights into the modulatory effects of propranolol in activated neutrophils, we performed RNA sequencing of immune complex-stimulated neutrophils in the absence and presence of the drug. We identified the transcriptomic signature of propranolol and demonstrated an ADR2-independent immunomodulatory effect. To determine if the anti-inflammatory transcriptomic signature of propranolol also translates into clinical effects, we next evaluated the impact of propranolol in a prototypical neutrophil-dependent skin disease, specifically, antibody transfer-induced epidermolysis bullosa acquisita in mice. To validate the identified propranolol gene signature obtained in human neutrophils, we analyzed a selection of genes by RT-PCR in mouse epidermolysis bullosa acquisita skin and confirmed TNF, among others, to be differentially regulated by propranolol treatment. Our data clearly indicate that, based on its molecular impact on immune complex-activated neutrophils, propranolol is a potential treatment option for neutrophil-mediated inflammatory skin diseases. |
| Databáze: | OpenAIRE |
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