Kaempferol inhibits NLRP3 inflammasome activation and pyroptosis to improve survival of sepsis mouse

doi:10.19871/j.cnki.xfcrbzz.2022.01.003

Abstract

Abstract: Objective To explore effects of kaempferol on ATP-induced NLRP3 inflammasome activation and pyroptosis in lipopolysaccharide(LPS)-primed murine bone marrow-derived macrophages and the underlying mechanism, and regulation of survival of sepsis mouse. Method The primary bone marrow cells of 6-7 week old C57BL/6 female mice were extracted and induced to differentiate into bone marrow-derived macrophages. According to the experimental design, they were divided into blank control group, LPS treatment group, drug treatment group, LPS+ATP group (positive model group), positive model dosing group (three drug concentrations). The NLRP3 inflammasome was activated by treating with LPS plus ATP. The protein levels of caspase-1p20, IL-1β and GSDMD were detected by Western blotting. Soluble IL-1β in the culture supernatants was measured by CBA assay. Cell death/pyroptosis was analyzed by propidium iodide (PI) staining. After adding protein kinase A (PKA) inhibitor H89, the above indicators of inflammasome activation and pyroptosis were detected again. Cecal ligation puncture (CLP) was used to establish septicemia mouse model. Result Kaempferol inhibited caspase-1p20 activation and mature IL-1β secretion in the LPS-primed BMDMs upon ATP treatment. Kaempferol also suppressed GSDMD-NT formation and pyroptosis in macrophages. In addition, H89 significantly reversed kaempferol-mediated suppression of ATP-induced caspase-1p20 activation, mature IL-1β secretion and pyroptosis. We also observed that Intragastric administration of kaempferol can effectively improve the survival rate of sepsis model mice. Conclusion Kaempferol probably suppressed NLRP3 inflammasome activation and pyroptosis through promoting PKA signaling in macrophages to improve the survival rate of sepsis mice.

Key words: Kaempferol, Inflammasome, Pyroptosis, Protein kinase A, Sepsis

Wu Senquan, Fang Xinnian, Mo Weiliang, Zhang Ping. Kaempferol inhibits NLRP3 inflammasome activation and pyroptosis to improve survival of sepsis mouse[J]. Electronic Journal of Emerging Infectious Diseases, 2022, 7(1): 12-16.

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