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Abstract
Pemphigoid diseases such as epidermolysis bullosa acquisita (EBA) may be difficult to treat. In pemphigoid diseases, mucocutaneous blistering is caused by autoantibodies to hemidesmosomal antigens; in EBA the autoantigen is type VII collagen. Despite growing insights into pemphigoid disease pathogenesis, corticosteroids are still a mainstay of treatment. In experimental EBA, myeloid cell activation is a key event leading to blistering. Activation of these cells depends on phosphodiesterase (PDE) 4. We therefore evaluated the potential for PDE4 inhibition in EBA: PDE4 was highly expressed in inflammatory cells and in the epidermis of patients compared with healthy skin samples. PDE4 inhibitors rolipram, roflumilast, and roflumilast N-oxide prevented the release of immune complex-induced reactive oxygen species from polymorphonuclear leukocytes and separation of the dermal-epidermal junction of skin incubated with antibodies to collagen type VII and polymorphonuclear leukocytes. The PDE4 inhibitors also impaired CD62L shedding and decreased CD11b expression on immune complex-stimulated polymorphonuclear leukocytes. For in vivo validation, experimental EBA was induced in mice by transfer of anti-collagen type VII IgG or immunization with collagen type VII. Roflumilast dose-dependently reduced blistering in antibody transfer-induced EBA and also hindered disease progression in immunization-induced EBA. PDE4 inhibition emerges as a new treatment modality for EBA and possibly other neutrophil-driven pemphigoid diseases.
Original language | English |
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Journal | Journal of Investigative Dermatology |
Volume | 136 |
Issue number | 11 |
Pages (from-to) | 2211-2220 |
Number of pages | 10 |
ISSN | 0022-202X |
DOIs | |
Publication status | Published - 01.11.2016 |
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Dive into the research topics of 'PDE4 Inhibition as Potential Treatment of Epidermolysis Bullosa Acquisita'. Together they form a unique fingerprint.Projects
- 1 Finished
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Dual contribution of the spleen tyrosine kinase (SYK) to epidermolysis bullosa acquisita pathogenesis
Ludwig, R. (Speaker, Coordinator), Samavedam, U. K. (Speaker, Coordinator), Recke, A. (Project Staff), Kauderer, C. (Project Staff) & Bieber, K. (Project Staff)
01.12.14 → 30.11.19
Project: DFG Projects › DFG Individual Projects