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FEBS Open Bio ; 10(8): 1482-1491, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32428336

RESUMEN

Sophora flavescens is used as a traditional herbal medicine to modulate inflammatory responses. However, little is known about the impact of (-)-maackiain, a compound derived from S. flavescens, on the activation of inflammasome/caspase-1, a key factor in interleukin-1ß (IL-1ß) processing. Here, we report that (-)-maackiain potently amplified caspase-1 cleavage in macrophages in response to nigericin (Nig). In macrophages primed with either lipopolysaccharide or monophosphoryl lipid A, Nig-mediated caspase-1 cleavage was also markedly promoted by (-)-maackiain. Notably, (-)-maackiain induced the production of vimentin, an essential mediator for the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome, thereby contributing to promotion of the formation of the inflammasome complex to activate caspase-1. Taken together, our data suggest that (-)-maackiain exerts an immunostimulatory effect by promoting IL-1ß production via activation of the inflammasome/caspase-1 pathway. Thus, the potent inflammasome-activating effect of (-)-maackiain may be clinically useful as an acute immune-stimulating agent.


Asunto(s)
Inflamasomas/efectos de los fármacos , Interleucina-1beta/biosíntesis , Extractos Vegetales/farmacología , Pterocarpanos/farmacología , Sophora/química , Animales , Células Cultivadas , Inflamasomas/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Nigericina/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Pterocarpanos/química , Pterocarpanos/aislamiento & purificación
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