4.7 Article

Expression and Regulation of the Proton-Coupled Oligopeptide Transporter PhT2 by LPS in Macrophages and Mouse Spleen

期刊

MOLECULAR PHARMACEUTICS
卷 11, 期 6, 页码 1880-1888

出版社

AMER CHEMICAL SOC
DOI: 10.1021/mp500014r

关键词

PhT2; macrophage; LPS; NF-kappa B; lysosome

资金

  1. Natural Scientific Foundation of China [81072689]
  2. National Major Projects for Science and Technology Development of Ministry Science and Technology of China [2012ZX09506001-004]
  3. NIH [R01-GM035498]

向作者/读者索取更多资源

Membrane transporter PhT2 (SLC15A3), which belongs to the proton-coupled oligopeptide transporter family, mediates the transport of di/tripeptides and histidine utilizing an inwardly directed proton gradient and negative membrane potential. The aim of this study was to elucidate the molecular expression of PhT2 in macrophages and mouse tissues and to explore the regulation of PhT2 by lipopolysaccharide (LPS). The results showed relatively high expression of PhT2 in J774A.1 and THP-1 macrophage cells, mouse spleen, and lung. Using an LPS-induced inflammatory cell model, we found that hPhT2 mRNA expression was up-regulated in THP-1 cells and that the up-regulation was suppressed by pyrrolidine dithiocarbamate, a specific inhibitor of NF-kappa B. Similar results were observed in mouse spleen during LPS-induced acute inflammation. Using dual-labeling immunofluorescence and confocal laser scanning microscopy, we confirmed that mPhT2 was colocalizing with lysosome-associated membrane protein 1 in transfected HEK293 cells. These results suggested that PhT2, a lysosomal membrane transporter, was pathway.

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