Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/radioterapia , Neoplasias Endometriales/radioterapia , Linfangioma/tratamiento farmacológico , Sirolimus/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias de la Vulva/tratamiento farmacológico , Administración Cutánea , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Femenino , Humanos , Linfangioma/etiología , Persona de Mediana Edad , Radioterapia/efectos adversos , Sirolimus/administración & dosificación , Neoplasias Cutáneas/etiología , Pared Torácica , Neoplasias de la Vulva/etiologíaAsunto(s)
Inmunosupresores/efectos adversos , Receptores Tipo II del Factor de Necrosis Tumoral/antagonistas & inhibidores , Escabiosis/etiología , Espondilitis Anquilosante/tratamiento farmacológico , Femenino , Humanos , Terapia de Inmunosupresión/efectos adversos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Antimicrobial peptides (AMPs) are a large family of peptides implicated in innate immunity, especially in the epidermis. Zinc gluconate has been proven to be efficient to treat inflammatory dermatoses, such as acne vulgaris. OBJECTIVES: The aim of our work was to determine whether AMPs could be new targets of zinc gluconate treatment in inflammatory dermatoses. MATERIAL AND METHODS: To test this hypothesis, we used an ex vivo lipopolysaccharide (LPS)-induced inflammatory skin explant model, with or without zinc gluconate pretreatment. We evaluated human ß-defensin-2 (hBD-2), human ß-defensin-4 (hBD-4) and psoriasin protein expression and release by immunohistochemistry and ELISA, as well as the mRNA expression level by quantitative PCR. RESULTS: We found that hBD-2 and psoriasin mRNA expression levels and hBD-2 extracellular release, but not hBD-4 expression and release, were significantly upregulated by zinc gluconate in LPS-stimulated inflammatory skin explants. CONCLUSION: These results suggest that hBD-2 and psoriasin may be two main targets of zinc gluconate, involved in its anti-inflammatory activity in dermatoses.
Asunto(s)
Gluconatos/farmacología , Proteínas S100/metabolismo , Piel/metabolismo , Regulación hacia Arriba/efectos de los fármacos , beta-Defensinas/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Técnicas In Vitro , Lipopolisacáridos/farmacología , ARN Mensajero/metabolismo , Proteína A7 de Unión a Calcio de la Familia S100 , Proteínas S100/genética , Piel/efectos de los fármacos , Estadísticas no Paramétricas , beta-Defensinas/genéticaRESUMEN
Peroxisome proliferator-activated receptors-α (PPARs-α) are nuclear receptors with anti-inflammatory properties. Zinc gluconate is efficient in the treatment of several inflammatory dermatoses. The aim of our work was to determine whether the modulation of PPAR-α expression and activity could be one of the mechanisms of action of zinc gluconate anti-inflammatory activity in inflammatory dermatoses. Thus, we used ex vivo skin explants incubated with lipopolysaccharide (LPS), a pro-inflammatory molecule, with or without zinc gluconate. We evaluated PPAR-α protein expression using immunohistochemistry, PPAR-α DNA-binding activity using an ELISA-like technique, and PPAR-α mRNA levels using quantitative PCR. On the one hand, we found that PPAR-α epidermal protein expression was stimulated by LPS and that LPS suppressed PPAR-α mRNA expression, without modifying its function. On the other hand, in inflammatory LPS-stimulated explants, zinc gluconate significantly upregulated PPAR-α function and mRNA expression level, without changing its epidermal protein expression. These results suggest that zinc gluconate may be a PPAR-α agonist, which might play a role in the anti-inflammatory activity of this molecule.