The Anti-Tumorigenic Mushroom Agaricus blazei Murill Enhances IL-1 beta Production and Activates the NLRP3 Inflammasome in Human Macrophages

作者：Huang Tsung Teng^*; Ojcius David M; Young John D; Wu Yi Hui; Ko Yun Fei; Wong Tsui Yin; Wu Cheng Yeu; Lu Chia Chen; Lai Hsin Chih

来源：PLos One, 2012, 7(7): e41383.

DOI：10.1371/journal.pone.0041383

Agaricus blazei Murill (AbM) has been reported to possess immune activity against tumors and infections through stimulation of mononuclear phagocytes. Recently, AbM extract was shown to induce the production of the pro-inflammatory cytokine, interleukin-1 beta (IL-1 beta), in human monocytes. IL-1 beta is a key pro-inflammatory cytokine produced by activated macrophages and monocytes and its secretion is strictly controlled by the inflammasome. The purpose of this study is to investigate the effect of AbM water extracts on the regulation of IL-1 beta production and activation of the NLRP3 inflammasome in human THP-1 macrophages. The NLRP3 inflammasome consists of an NLRP3 receptor, an adaptor protein called ASC, and the inflammatory protease, caspase-1. Typically, stimulation of immune cells with microbial products results in production of pro-IL-1 beta, but a second stress-related signal activates the inflammasome and caspase-1, leading to processing and secretion of IL-1 beta. Our results show that AbM enhances transcription of IL-1 beta and triggers NLRP3 inflammasome-mediated IL-1 beta secretion in human THP-1 macrophages. AbM-mediated IL-1 beta secretion was markedly reduced in macrophages deficient in NLRP3 and ASC, demonstrating that the NLRP3 inflammasome is essential for AbM-induced IL-1 beta secretion. In addition, caspase-1 was activated and involved in proteolytic cleavage and secretion of IL-1 beta in AbM-treated macrophages. AbM-mediated IL-1 beta secretion also decreased in cells treated with cathepsin B inhibitor, suggesting that AbM can induce the release of cathepsin B. Furthermore, our data show that AbM-induced inflammasome activation requires the release of ATP, binding of extracellular ATP to the purinergic receptor P2X(7), the generation of reactive oxygen species, and efflux of potassium. Taken together, these findings reveal that AbM activates the NLRP3 inflammasome via multiple mechanisms, resulting in the secretion of IL-1 beta.

• 出版日期2012-7-23
• 单位长春大学