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PLoS One ; 11(4): e0153090, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27078876

RESUMEN

Envenomation by Loxosceles spider is characterized by the development of dermonecrosis. In previous studies, we have demonstrated that increased expression/secretion of matrix metalloproteinases 2 and 9, induced by Loxosceles intermedia venom Class 2 SMases D (the main toxin in the spider venom), contribute to the development of cutaneous loxoscelism. In the present study we show that the more potent venom containing the Class 1 SMase D from Loxosceles laeta, in addition to increasing the expression/secretion of MMP2 and MMP9, also stimulates the expression of MMP7 (Matrilysin-1), which was associated with keratinocyte cell death. Tetracycline, a matrix metalloproteinase inhibitor, prevented cell death and reduced MMPs expression. Considering that L. laeta venom is more potent at inducing dermonecrosis than L. intermedia venom, our results suggest that MMP7 may play an important role in the severity of dermonecrosis induced by L. laeta spider venom SMase D. In addition, the inhibition of MMPs by e.g. tetracyclines may be considered for the treatment of the cutaneous loxoscelism.


Asunto(s)
Proteínas de Artrópodos/farmacología , Queratinocitos/efectos de los fármacos , Hidrolasas Diéster Fosfóricas/farmacología , Venenos de Araña/farmacología , Arañas/enzimología , Animales , Antibacterianos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Queratinocitos/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 7 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Necrosis/prevención & control , Conejos , Piel/efectos de los fármacos , Piel/patología , Venenos de Araña/enzimología , Tetraciclina/farmacología , Factores de Tiempo
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