Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering skin disease characterized by autoantibodies against the hemidesmosomal proteins BP180 and BP230. The cell stress chaperone heat shock protein 90 (Hsp90) has been implicated in inflammatory responses, and recent evidence suggests that it represents a novel treatment target in autoimmune bullous diseases. The aim of the study was to investigate the contribution of Hsp90 to the proinflammatory cytokine production in keratinocytes induced by autoantibodies to BP180 from BP patient serum. HaCaT cells were treated with purified human BP or normal IgG in the absence or presence of the Hsp90 blocker 17-DMAG and effects on viability, interleukin 6 (IL-6) and IL-8 (cytokines critical for BP pathology), NFκB (their major transcription factor), and Hsp70 (marker of effective Hsp90 inhibition and potent negative regulator of inflammatory responses) were investigated. We found that BP IgG stimulated IL-6 and IL-8 release from HaCaT cells and that non-toxic doses of 17-DMAG inhibited this IL-8, but not IL-6 secretion in a dose-and time-dependent fashion.
Although the results of this study are based on autoantibodies prepared from a single patient, they show that calcitriol protects from BP IgG-induced inflammatory processes in vitro, thus favouring its potential inclusion into the therapeutic repertoire of BP.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.