DELPHINIDIN INDUCES EPIDERMAL DIFFERENTIATION AND INHIBITS PROLIFERATION AND INFLAMMATION IN A THREE-DIMENSIONAL RECONSTITUTED SKIN MODEL OF PSORIASIS.
Psoriasis is a chronic, inflammatory skin disease characterized by epidermal hyperproliferation and aberrant keratinocyte differentiation. Several lines of evidence suggest that intrinsic alterations of the epidermis may play an important role in the pathogenesis of psoriasis. Identification of natural agents that possess the ability to abrogate these effects could be useful for the treatment of this disease. Delphinidin, present in pigmented fruits and vegetables, possesses potent antioxidant and anti-inflammatory activities. In this study, we examined the effect of delphinidin on markers of epidermal differentiation, proliferation and inflammation by employing three-dimensional models of reconstituted normal and psoriatic human skin. Delphinidin (5-20 μM; 2-8 days) treatment of reconstituted human skin increased the processing of caspase-14, protein expression of transglutaminase-1, involucrin, loricrin and filaggrin in a dose- and time-dependent manner. In addition, delphinidin treatment induced terminal differentiation resulting in more rapid formation of cornified envelopes without inducing apoptosis. Next, studies were performed to establish the significance of these findings by employing a three-dimensional reconstituted skin model of psoriasis. Psoriasis is characterized by down-regulation of differentiation markers, including caspase-14 and filaggrin, and by upregulation of markers of proliferation (Ki67 and PCNA) and inflammation (iNOS) in the epidermis. Employing immunohistochemical analysis, we found that treatment of psoriatic tissues with delphinidin resulted in an increased expression of caspase-14 and filaggrin. In addition, delphinidin treatment reduced these markers of cell proliferation and inflammation. We suggest that delphinidin could be a promising agent for treatment of psoriasis.
Anthocyanidin, Caspase-14, Cell proliferation, Filaggrin, Inflammation, iNOS, Ki67, Loricrin, PCNA, Procaspase-3, Procaspase-8, Procaspase-9, proliferation, Psoriasis, Psoriatic human skin model, Psoriatic tissue models (PTM), SOR-300-FT, Transglutaminase 1
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