Calcitriol exerts anti-inflammatory effects in keratinocytes treated with autoantibodies from a patient with bullous pemphigoid.

BACKGROUND: The hormonally active vitamin D metabolite calcitriol and its analogues exert potent effects on cellular differentiation and regulation of immune responses. Although topical vitamin D analogues are widely used for treatment of psoriasis and vitamin D has been increasingly implicated in prevention and protection from several autoimmune diseases, experimental and clinical data in autoimmune bullous diseases are generally lacking.OBJECTIVE: Here, we investigated the effects of calcitriol on keratinocytes treated by bullous pemphigoid (BP) autoantibodies.METHODS: Human keratinocyte (HaCaT) cells were treated with purified human BP or normal IgG from one BP patient and healthy subject, respectively, in the absence or presence of calcitriol and effects on (i) cell viability, (ii) IL-6 and IL-8 secretion, (iii) STAT3 and NFκB activation, (iv) heat shock protein 70 (Hsp70) level, and (v) vitamin D receptor (VDR) expression were studied.RESULTS: We found that BP IgG-induced IL-6 and IL-8 release from HaCaT cells was reduced in the presence of non-toxic doses of calcitriol. Additionally, calcitriol blunted BP IgG-mediated STAT3 phosphorylation and NFκB activity, whereas Hsp70 and VDR expression were not affected.CONCLUSION: 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.