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

ABSTRACT: 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 (pM?s) is correlated with enhanced production of IL-6 and TNF-? 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 pM?s 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.

SUBMITTER: Pan H

PROVIDER: S-EPMC4741706 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other

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

Pan Hao H Xu Li-Hui LH Huang Mei-Yun MY Zha Qing-Bing QB Zhao Gao-Xiang GX Hou Xiao-Feng XF Shi Zi-Jian ZJ Lin Qiu-Ru QR Ouyang Dong-Yun DY He Xian-Hui XH

Oncotarget 20151001 32

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 aci ...[more]

PMID: 26439699

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Project description:Background/aimThe uveal compartment of the eye contains extensive networks of resident macrophages and dendritic cells. These cells are now recognised to have a role in many ocular pathologies. The aim of this study was to isolate, characterise, and compare the function of ciliary body/choroid dendritic cells and macrophages from the normal eye.MethodsExplants of rat and human ciliary body/choroid were cultured in vitro for various periods of time and cells harvested either from the supernatant fluid or from enzyme digested and washed explants. The cells were then phenotyped by microscopy and flow cytometry, examined by video time lapse photomicroscopy, and analysed functionally in a series of immunoassays.ResultsTwo main types of dendritic cell were identified: large veil-like MHC class II(mid) motile but relatively non-translocatory cells and small MHC class II(hi) motile and rapidly translocating cells. Tissue macrophages mainly remained associated with the explants in culture but gradually lost their resident tissue marker (ED2) and detached from the explants as clusters of low density, large, CR3 (ED7)(+) cells, some of which underwent apoptosis. Video time lapse studies showed dendritic cells constantly interacting with large single cells and cell clusters by traversing the interstices of the cell clusters. In functional studies, freshly isolated dendritic cells were poor presenters of antigen and required activation by short term culture for acquisition of antigen presenting function. In contrast, dendritic cell depleted choroidal cell preparations containing macrophages and other cells failed to present antigen even after short term culture but augmented the antigen presenting function of dendritic cells when tested in co-culture.ConclusionAt least two types of dendritic cells are present in the normal ciliary body/choroid layer of the eye. It is likely that these cells have different functions based on their motility and potential to migrate to secondary lymphoid tissue either during normal physiological homeostatic processes or during an inflammatory response. The behaviour of resident tissue myeloid cells may decide the outcome of the organism's response to stress, foreign antigen, and ageing processes such as age related macular degeneration.

Dataset Information

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

Publications

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

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