Autoantibodies to BP180 associated with bullous pemphigoid release interleukin-6 and interleukin-8 from cultured human keratinocytes

Enno Schmidt, Stanislaus Reimer, Niels Kruse, Silke Jainta, Eva Bettina Bröcker, M. Peter Marinkovich, George J. Giudice, Detlef Zillikens*

*Corresponding author for this work
101 Citations (Scopus)


Bullous pemphigoid is an inflammatory subepiderreal blistering disease that is associated with autoantibodies 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-1α, interleukin-1β, tumor necrosis factor-α, 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.

Original languageEnglish
JournalJournal of Investigative Dermatology
Issue number5
Pages (from-to)842-848
Number of pages7
Publication statusPublished - 2000

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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