Maackiain, a compound derived from <i>Sophora flavescens</i>, increases IL‐1β production by amplifying nigericin‐mediated inflammasome activation
Jin-Won Huh, Jung‐Hoon Lee, Eekhyoung Jeon, Hyung Won Ryu, Sei‐Ryang Oh, Kyung‐Seop Ahn, Hyun Sik Jun, Un‐Hwan Ha
Abstract
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-1β (IL-1β) 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-1β 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.