title: Expression and regulation of the proton-coupled oligopeptide transporter PhT2 by LPS in macrophages and mouse spleen.
abstract: 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-κB. 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 up-regulated by LPS via the NF-κB signaling pathway.
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou, Zhejiang 310058, P. R. China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Dongli
authors.initials: D
authors.lastname: Sun
authors.forename: Feifeng
authors.initials: F
authors.lastname: Song
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Hu
authors.forename: David E
authors.initials: DE
authors.lastname: Smith
authors.forename: Huidi
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics; D011522:Protons; D015398:Signal Transduction / Q000235:genetics; D013154:Spleen / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D008070:Lipopolysaccharides; D051907:Lysosomal Membrane Proteins; D026901:Membrane Transport Proteins; D016328:NF-kappa B; D009842:Oligopeptides; D011522:Protons
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