Research Papers: Immunology:

Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection

Hao Pan, Li-Hui Xu, Mei-Yun Huang, Qing-Bing Zha, Gao-Xiang Zhao, Xiao-Feng Hou, Zi-Jian Shi, Qiu-Ru Lin, Dong-Yun Ouyang _ and Xian-Hui He

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Oncotarget. 2015; 6:32468-32483. https://doi.org/10.18632/oncotarget.5957

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Hao Pan1,*, Li-Hui Xu2,*, Mei-Yun Huang1, Qing-Bing Zha3, Gao-Xiang Zhao1, Xiao-Feng Hou1, Zi-Jian Shi3, Qiu-Ru Lin1, Dong-Yun Ouyang1 and Xian-Hui He1

1 Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China

2 Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China

3 Department of Fetal Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, China

* These authors have contributed equally to this work

Correspondence to:

Dong-Yun Ouyang, email:

Xian-Hui He, email:

Keywords: bacterial infection, mTORC1, peritoneal macrophages, piperine, SLC7A5/SLC3A2, Immunology and Microbiology Section, Immune response, and Immunity

Received: July 07, 2015 Accepted: September 12, 2015 Published: October 02, 2015


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.

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