Protective effect of Ketone musk on LPS/ATP-induced pyroptosis in J774A.1 cells through suppressing NLRP3/GSDMD pathway.

Pyroptosis is a different type of proinflammatory and lytic mode of cell death from apoptosis and necrosis, which play a killer and cleaner to the pathogenic microorganisms as an immune response when the host is infected by pathogenic microorganisms. Ketone musk (KM) is a component of the native musk, which is widely used to medicine and chemical engineering. In this research, we studied whether KM can suppress the pyroptosis in J774A.1 cells induced by lipopoysaccharide (LPS)/Adenosine Triphosphate (ATP) stimulation. The results showed that KM increased the viability of LPS/ATP-stimulated cells, decreased the production of interleukin (IL)-1β/18, and suppressed the activation of caspased-1 and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and gasdermin D (GSDMD). Our present study demonstrated that KM inhibited LPS/ATP-induced pyroptosis and the release of IL-1β/18 in J774A.1 cells by inhibiting the activation of GSDMD and caspase-1 and the assembly of NLRP3 inflammasome. Our finding may be of significance on investigating that KM has a positive potential application in the treatment of pyroptosis-mediated diseases.