Evidence map›Paper›PMID 29991810›Full record

ArticleCell death & disease2018

Regulation and biological role of the peptide/histidine transporter SLC15A3 in Toll-like receptor-mediated inflammatory responses in macrophage.

Feifeng Song, Yaodong Yi, Cui Li, Yongjun Hu, Jinhai Wang, David E Smith, Huidi Jiang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
1.2field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 64 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Feifeng SongLaboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Yaodong YiLaboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Cui LiLaboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Yongjun HuDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109, United States.ORCID 0000-0002-1883-0868
Jinhai WangThe First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
David E SmithDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109, United States.
Huidi JiangLaboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China. hdjiang@zju.edu.cn.
Zhejiang University · CNUniversity of Michigan · US

Funding

Novel Transport and Activation Strategy to Improve the Bioavailability of Targeted ProdrugsR01GM115481 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AMIDON, GORDON L, SMITH, DAVID E · 2015 to 2018
$1.7M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01GM115481National Natural Science Foundation of China (National Science Foundation of China) 81573492NIGMS NIH HHS R01 GM115481
6 · The paper itself

Abstract

The peptide/histidine transporter SLC15A3 is responsible for transporting histidine, certain dipeptide and peptidomimetics from inside the lysosome to cytosol. Previous studies have indicated that SLC15A3 transcripts are mainly expressed in the lymphatic system, however, its regulation and biological role in innate immune responses and inflammatory diseases are as yet unknown. In this study, mouse peritoneal macrophages (PMs), mouse bone marrow-derived macrophages (BMDMs), the human acute monocytic leukemia cell line THP-1 and the human lung epithelial carcinoma cell line A549 were used to investigate the regulation and biological role of SLC15A3 in TLR-mediated inflammatory responses. Our results showed that SLC15A3 was upregulated by TLR2, TLR4, TLR7 and TLR9 ligands in macrophages at both the mRNA and protein levels via activation of NF-κB (nuclear factor-kappa-B), MAPK (mitogen-activated protein kinase) and IRF3 (interferon regulatory factor 3). Furthermore, knockdown or overexpression of SLC15A3 influenced the TLR4-triggered expression of proinflammatory cytokines. A reporter gene assay showed that the SLC15A3 promotor contained potential NF-κB binding sites, which were reasonable for regulating SLC15A3 by TLR-activation through NF-κB signaling. Additionally, SLC15A3 expression was increased and positively related to inflammation in mice with bacterial peritonitis. The collective findings suggest that SLC15A3 is regulated by various TLRs, and that it plays an important role in regulating TLR4-mediated inflammatory responses.

Indexed as

A549 CellsAnimalsCell LineCells, CulturedHumansInterferon Regulatory Factor-3MacrophagesMaleMembrane Transport ProteinsMiceMitogen-Activated Protein KinasesPathogen-Associated Molecular Pattern MoleculesPeritonitisTHP-1 CellsToll-Like Receptor 2Toll-Like Receptor 4Interferon Regulatory Factor-3Membrane Transport ProteinsMitogen-Activated Protein KinasesPathogen-Associated Molecular Pattern MoleculesSLC15A3 protein, humanSLC15A3 protein, mouseToll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptor 7Toll-Like Receptor 9Toll-Like Receptors

Identifiers

PMID29991810
PMCPMC6039463
OpenAlexW2821171282

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.