Vitamin K3 suppresses pyroptosis in THP-1 cells through inhibition of NF-κB and JNK signaling pathways.

Abstract

Vitamin K, a necessary nutritional supplement for human, has been found to exhibit anti-inflammatory activity. In the present study, we investigated the effects of vitamin K family on lipopolysaccharide (LPS) plus nigericin induced pyroptosis and explored the underlying mechanism of its action in THP-1 monocytes. Results showed that vitamin K3 treatment significantly suppressed THP-1 pyroptosis, but not vitamin K1 or K2, as evidenced by increased cell viability, reduced cellular LDH release and improved cell morphology. Vitamin K3 inhibited NLRP3 expression, caspase-1 activation, GSDMD cleavage and IL-1β secretion in pyrophoric THP-1 cells. In addition, vitamin K3 inhibited the pro-inflammatory signaling pathways including NF-κB and JNK. Vitamin K3 treatment also attenuated tissue damage and reduced serum LDH, IL-1β and IL-6 levels in LPS-induced systemic inflammation of mice. The reduced MPO activityand F4/80 expression indicated that vitamin K3 effectively reduced the infiltration of neutrophils and macrophages. Moreover, NLRP3 expression in monocytes/macrophages were also decreased in vitamin K3-treatedmice after LPS challenge. These findings suggest that vitamin K3 potently alleviates systemic inflammation and organ injury via inhibition of pyroptosis in monocytes and may serve as a novel therapeutic strategy for patients with inflammatory diseases.