Maackiain, a compound derived from Sophora flavescens, increases IL‐1β production by amplifying nigericin‐mediated inflammasome activation. Issue 8 (26th June 2020)

• Record Type: Journal Article
• Authors: Huh, Jin‐Won; Lee, Jung‐Hoon; Jeon, Eekhyoung; Ryu, Hyung Won; Oh, Sei‐Ryang; Ahn, Kyung‐Seop; Jun, Hyun Sik; Ha, Un‐Hwan
• Is Part Of: FEBS open bio. Volume 10:Issue 8(2020)
• Page Start: 1482
• Page End: 1491
• Publication Date: 2020-06-26
• Subjects: (‐)‐maackiain -- inflammasome -- monophosphoryl lipid A -- nigericin -- Sophora flavescens; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12899
• Languages: English
• ISSNs: 2211-5463

Abstract

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. Abstract : Proinflammatory cytokine interleukin‐1β (IL‐1β) plays critical roles in defending against infections. Sophora flavescens ‐derived (‐)‐maackiain potently amplifies caspase‐1 cleavage in response to nigericin. Notably, (‐)‐maackiain promotes caspase‐1 cleavage and IL‐1β production even in monophosphoryl lipid A‐primed macrophages. The potent inflammasome‐activating effect of (‐)‐maackiain may be clinically useful as an acute immune‐stimulating agent.