Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection.
Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection.
复制标题
胡椒碱通过代谢调节腹膜驻留巨噬细胞，增强其抵抗细菌感染的功能
DOI：
10.18632/oncotarget.5957
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发表时间：
2015-10-20
期刊：
影响因子：
--
通讯作者：
He XH
中科院分区：
文献类型：
--
作者：
Pan H;Xu LH;Huang MY;Zha QB;Zhao GX;Hou XF;Shi ZJ;Lin QR;Ouyang DY;He XH
胡椒是一种日常使用的食欲调味品，在民间医学中被广泛用于治疗胃肠道疾病。胡椒碱是辣椒中的主要生物碱，具有广泛的药理活性。然而，胡椒碱的代谢和药用活性之间的联系机制仍不清楚。在这里，我们报道胡椒碱通过招募更多的L1系统氨基酸转运蛋白(SLC7A5/SLC3A2)到细胞膜，从而促进氨基酸代谢，从而有力地促进mTORC1的活性。胡椒碱诱导的常驻腹膜巨噬细胞(PM、Φ、S)mTORC_1活性的增加与内毒素刺激下IL-6和肿瘤坏死因子-α的产生增加有关。这种细胞因子产生的增强可以被mTOR信号通路的抑制剂所消除，这表明mTOR在这一过程中发挥了作用。此外，胡椒碱治疗还保护了PMΦS免受细菌诱导的细胞凋亡和消失，并提高了他们的细菌吞噬能力。因此，胡椒碱使小鼠对细菌感染甚至败血症具有抵抗力。我们的数据强调，胡椒碱有能力代谢重新编程腹膜常驻巨噬细胞，以加强其固有功能，以抵御细菌感染。
Pepper, a daily-used seasoning for promoting appetite, is widely used in folk medicine for treating gastrointestinal diseases. Piperine is the major alkaloid in pepper and possesses a wide range of pharmacological activities. However, the mechanism for linking metabolic and medicinal activities of piperine remains unknown. Here we report that piperine robustly boosts mTORC1 activity by recruiting more system L1 amino acid transporter (SLC7A5/SLC3A2) to the cell membrane, thus promoting amino acid metabolism. Piperine-induced increase of mTORC1 activity in resident peritoneal macrophages (pMΦs) is correlated with enhanced production of IL-6 and TNF-α upon LPS stimulation. Such an enhancement of cytokine production could be abrogated by inhibitors of the mTOR signaling pathway, indicating mTOR's action in this process. Moreover, piperine treatment protected resident pMΦs from bacterium-induced apoptosis and disappearance, and increased their bacterial phagocytic ability. Consequently, piperine administration conferred mice resistance against bacterial infection and even sepsis. Our data highlight that piperine has the capacity to metabolically reprogram peritoneal resident macrophages to fortify their innate functions against bacterial infection.