Methods: Filaggrin expression was measured in skin biopsies from 42 persons with AD and 36 with normal skin and cultured keratinocytes . PP concentration in the culture medium made up 10-2 -10-6. Immunohistochemical and Western blotting methods were used to detect the changes in the expression levels of filaggrin and DPAGT1. IL-4 and IL-13 was determined using ELISA. Intermediates of DPC fractions were analysed by HPLC method.
Results: Overexpression of DPAGT1 was 5-fold higher in AD skin biopsies than in normal skin biopsies. AD cells differ from normal one in filaggrin content lost by 3-4 times. IL-4 and IL-13 cause overexpression and abberant N-glycosylation of filaggrin in DPC. The study showed overexpression of DPAGT1 and 6-fold DPC intermediates decrease in keratinocytes in presence of IL-13 and 2-fold in presence of IL-4 cells. Treatment of keratinocytes with PP resulted in downregulation of DPAGT1. It is established that PP in the concentration 10-2 M could overcome DPAGT1 overexpression which leads to regulation of filaggrin N-glycosylation.
Conclusions: IL-13 could cause DPAGT overexpression and dysregulation of N-glycosylation in keratinocytes which leads to AD fenotype affecting the stability of tight assembly and adherence junctions in skin. The findings indicate that DPAGT1 overexpression in keratinocytes treated with IL-4 and IL-13 can be overcomed by PP, which provides a DolP substitute for DPAGT1 normal expression, N-glycosylation and filaggrin loss prevention without neutralization of interleukins. Polyprenol could be a promising agent for atopic dermatis prevention and control.