Autoantibodies to BP180 Associated with Bullous Pemphigoid Release Interleukin-6 and Interleukin-8 from Cultured Human Keratinocytes
| Autor: | Enno Schmidt, Stanislaus Reimer, Silke Jainta, Eva-Bettina Bröcker, Detlef Zillikens, Niels Kruse, M. Peter Marinkovich, George J. Giudice |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Keratinocytes
Pemphigoid medicine.medical_treatment mRNA Dermatology Autoantigens Biochemistry Epitope Pemphigoid Bullous Medicine RNA Messenger Interleukin 8 skin and connective tissue diseases Molecular Biology Cells Cultured Autoantibodies integumentary system Interleukin-6 business.industry Interleukin-8 autoimmunity Cell Biology Non-Fibrillar Collagens epitopes medicine.disease eye diseases cytokines Protein Structure Tertiary Up-Regulation Cytokine medicine.anatomical_structure Ectodomain Immunoglobulin G Immunology Tumor necrosis factor alpha Bullous pemphigoid business Keratinocyte |
| Zdroj: | Journal of Investigative Dermatology. (5):842-848 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2000.00141.x |
| Popis: | Bullous pemphigoid is an inflammatory subepidermal blistering disease that is associated with auto- antibodies to the keratinocyte surface protein, BP180. In addition to the binding of autoantibodies, the infiltration of inflammatory cells is necessary for blister formation. Cytokines, including interleukin-6 and interleukin-8, have been implicated in the disease process of both human and experimental murine bullous pemphigoid. This study was aimed at testing the hypothesis that the binding of anti-BP180 antibodies to their target antigen triggers a signal transduction event that results in the secretion of these pro-inflammatory cytokines. Consistent with this hypothesis, treatment of cultured normal human epidermal keratinocytes with bullous pemphigoid IgG, but not control IgG, led to increased levels of interleukin-6 and interleukin-8, but not interleukin-1alpha, interleukin-1beta, tumor necrosis factor-alpha, interleukin-10, or monocyte chemoattractant protein-1, in the culture medium. This effect was concentration- and time-dependent and was abolished by depleting the bullous pemphigoid IgG of reactivity to two distinct epitopes on the BP180 NC16A domain. Upregulation of interleukin-6 and interleukin-8 was found at both protein and mRNA levels. In addition, bullous pemphigoid IgG did not induce the release of interleukin-6 and interleukin-8 from BP180-deficient keratinocytes obtained from a patient with generalized atrophic benign epidermolysis bullosa. These data indicate that bullous pemphigoid-associated autoantibodies to the human BP180 ectodomain trigger a signal transducing event that leads to expression and secretion of interleukin-6 and interleukin-8 from human keratinocytes. |
| Databáze: | OpenAIRE |
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