Propranolol Is an Effective Topical and Systemic Treatment Option for Experimental Epidermolysis Bullosa Acquisita.

Abstract

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.

• Authors: Pia Stüssel, Katharina Schulze Dieckhoff, Sven Künzel, Veronika Hartmann, Yask Gupta, Georg Kaiser, Wendelien Veldkamp, Gestur Vidarsson, Remco Visser, Saeedeh Ghorbanalipoor, Kazuko Matsumoto, Malin Krause, Frank Petersen, Kathrin Kalies, Ralf J Ludwig, Katja Bieber
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 140 Issue 12 Pg. 2408-2420 (12 2020) ISSN: 1523-1747 [Electronic] United States
• PMID: 32450072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic beta-Antagonists
• Receptors, Adrenergic
• Propranolol

Topics

• Administration, Cutaneous
• Administration, Oral
• Adrenergic beta-Antagonists (administration & dosage)
• Animals
• Cells, Cultured
• Chemotaxis, Leukocyte (drug effects)
• Disease Models, Animal
• Epidermolysis Bullosa Acquisita (drug therapy, immunology, pathology)
• Healthy Volunteers
• Humans
• Mice
• Neutrophils (drug effects, immunology)
• Primary Cell Culture
• Propranolol (administration & dosage)
• RNA-Seq
• Receptors, Adrenergic (metabolism)
• Signal Transduction (drug effects, immunology)
• Skin (drug effects, pathology)
• Transcriptome (drug effects, immunology)