α-Mangostin suppresses NLRP3 inflammasome activation via promoting autophagy in LPS-stimulated murine macrophages and protects against CLP-induced sepsis in mice
The major mechanism of sepsis is immunosuppression caused by host response dysfunction. It has been found that α-Mangostin (α-M) is a potential candidate as a treatment for multiple inflammatory and immune disorders. To date, the role of α-M in host response during sepsis remains unexplored.
Methods and results
Herein, we examined the effect of α-M on macrophages-mediated host response in the presence of lipopolysaccharide (LPS), and the vital organ function, inflammatory response, and survival rate in septic mice. In murine peritoneal macrophages, α-M induced autophagy and then inhibited LPS-stimulated NLRP3 inflammasome activation, as well as interleukin-1β (IL-1β) production. Moreover, α-M improved phagocytosis and killing of macrophages, and increased M2 macrophages numbers after LPS stimulation. Furthermore, in vivo experiment suggested that α-M reduced serum levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1β, alanine transaminase (ALT), aspartate transaminase (AST), and creatinine (Cr), whilst increased that of interleukin-10 (IL-10) in caecal ligation and puncture (CLP) mice.
Taken together, these findings showed that α-M-mediated macrophages autophagy contributed to NLRP3 inflammasome inactivation and α-M exerted organ protection in septic mice.
Keywordsα-Mangostin Sepsis Macrophages Autophagy NLRP3 inflammasome
YG, MH guaranteed integrity of the entire study. YG designed the research, wrote the paper, analyzed the data. XX, QL,YX conducted experiments. MH contributed to revise the paper. All authors critically reviewed the manuscript for important intellectual content and approved the final version.
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