RESUMO
In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen-potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2-P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT-induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding.
Assuntos
Alopecia/prevenção & controle , Butiratos/farmacologia , Derme/efeitos dos fármacos , Di-Hidrotestosterona/farmacologia , Folículo Piloso/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Alopecia/induzido quimicamente , Alopecia/genética , Alopecia/patologia , Androgênios/efeitos adversos , Ácido Ascórbico/metabolismo , Butiratos/metabolismo , Células Cultivadas , Quimioprevenção/métodos , Técnicas de Cocultura , Derme/metabolismo , Derme/patologia , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , MasculinoRESUMO
Mast cell-mediated allergic symptoms are involved in many diseases, such as asthma and sinusitis. In this study, we investigated the effect of ethanol extract of fruits of Prunus persica (L) Batsch (FPP) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. FPP dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated local allergic reactions. Histamine releasing from mast cells was reduced by FPP, which was mediated by modulation of intracellular calcium. In addition, FPP attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of FPP on pro-inflammatory cytokines was nuclear factor (NF)-kappaB dependent. Our findings provide evidence that FPP inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects.