piperine and Escherichia-coli-Infections

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.

Topics: Alkaloids; Amino Acids; Animals; Anti-Bacterial Agents; Apoptosis; Benzodioxoles; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Female; Fusion Regulatory Protein 1, Heavy Chain; HeLa Cells; Humans; Immunity, Innate; Inflammation Mediators; Interleukin-6; Large Neutral Amino Acid-Transporter 1; Lipopolysaccharides; Macrophage Activation; Macrophages, Peritoneal; Male; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Inbred C57BL; Multiprotein Complexes; Phagocytosis; Piperidines; Polyunsaturated Alkamides; RAW 264.7 Cells; RNA Interference; Signal Transduction; Time Factors; TOR Serine-Threonine Kinases; Transfection; Tumor Necrosis Factor-alpha