Comparative effects of schisandrin A, B, and C on Propionibacterium acnes-induced, NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis

Abstract

Propionibacterium acnes, a common pathogen associated with acne, is also responsible for various surgical infections. Schisandrin A, schisandrin B and schisandrin C, the representative lignans of Schisandra chinensis (Turcz.) Baill. extract, inhibit P. acnes-induced inflammation. However, their effects on P. acnes-induced IL-1β secretion and pyroptosis mediated by NLRP3 inflammasome activation remain unknown. In this study, we compared the effects of schisandrin A, B, and C (Sch A, B, and C) on IL-1β secretion and pyroptosis in P. acnes-infected THP-1 cells. As NLRP3 plays important roles in P. acnes-mediated inflammation and pyroptosis, we also investigated the effects of Schs on P. acnes-induced NLRP3 inflammasome activation by measuring the levels of NLRP3, active caspase-1, and mature IL-1β, and activity of caspase-1. Our results showed that Sch A, B, and C suppressed P. acnes-induced pyroptosis. Further, the three lignans significantly suppressed NLRP3 inflammasome activation, with the following potency: Sch C > Sch B > Sch A. Three lignans also inhibited the production of mitochondrial ROS and ATP release. Additionally, Sch B and C almost completely prevented the efflux of K^+., whereas Sch A had a relatively weak effect. Collectively, our novel findings showed that Sch A, B, and C effectively suppressed IL-1β secretion and pyroptosis by inhibiting NLRP3 inflammasome activation in P. acnes-infected THP-1 cells. Thus, Schs may be promising agents for the treatment of P. acnes-related infections.

Keywords: Anti-inflammatory; Caspase-1; NLRP3 inflammasome; Propionibacterium acnes; Pyroptosis; Schisandrin.