Evidence map›Paper›PMID 26787872›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

LDL receptor-related protein-1 regulates NFκB and microRNA-155 in macrophages to control the inflammatory response.

Elisabetta Mantuano, Coralie Brifault, Michael S Lam, Pardis Azmoon, Andrew S Gilder, Steven L Gonias

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 2 pooled it
6.5field-weighted citation impact, top 3% 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

85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 153 citations in OpenAlex.

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25 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Elisabetta MantuanoDepartment of Pathology, University of California San Diego, La Jolla, CA 92093; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Coralie BrifaultDepartment of Pathology, University of California San Diego, La Jolla, CA 92093;
Michael S LamDepartment of Pathology, University of California San Diego, La Jolla, CA 92093;
Pardis AzmoonDepartment of Pathology, University of California San Diego, La Jolla, CA 92093; Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Andrew S GilderDepartment of Pathology, University of California San Diego, La Jolla, CA 92093;
Steven L GoniasDepartment of Pathology, University of California San Diego, La Jolla, CA 92093; sgonias@ucsd.edu.
University of California, San Diego · USSapienza University of Rome · IT

Funding

REGULATION OF UROKINASE RECEPTOR ACTIVITY BY LRPR01HL060551 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GONIAS, STEVEN L. · 1999 to 2014
$4.0M
NHLBI NIH HHS R01 HL060551NHLBI NIH HHS R01 HL60551
6 · The paper itself

Abstract

LDL receptor-related protein-1 (LRP1) is an endocytic and cell-signaling receptor. In mice in which LRP1 is deleted in myeloid cells, the response to lipopolysaccharide (LPS) was greatly exacerbated. LRP1 deletion in macrophages in vitro, under the control of tamoxifen-activated Cre-ER(T) fusion protein, robustly increased expression of proinflammatory cytokines and chemokines. In LRP1-expressing macrophages, proinflammatory mediator expression was regulated by LRP1 ligands in a ligand-specific manner. The LRP1 agonists, α2-macroglobulin and tissue-type plasminogen activator, attenuated expression of inflammatory mediators, even in the presence of LPS. The antagonists, receptor-associated protein (RAP) and lactoferrin (LF), and LRP1-specific antibody had the entirely opposite effect, promoting inflammatory mediator expression and mimicking LRP1 deletion. NFκB was rapidly activated in response to RAP and LF and responsible for the initial increase in expression of proinflammatory mediators. RAP and LF also significantly increased expression of microRNA-155 (miR-155) after a lag phase of about 4 h. miR-155 expression reflected, at least in part, activation of secondary cell-signaling pathways downstream of TNFα. Although miR-155 was not involved in the initial induction of cytokine expression in response to LRP1 antagonists, miR-155 was essential for sustaining the proinflammatory response. We conclude that LRP1, NFκB, and miR-155 function as members of a previously unidentified system that has the potential to inhibit or sustain inflammation, depending on the continuum of LRP1 ligands present in the macrophage microenvironment.

Indexed as

AnimalsInflammationLigandsLow Density Lipoprotein Receptor-Related Protein-1MacrophagesMiceMicroRNAsNF-kappa BLigandsLow Density Lipoprotein Receptor-Related Protein-1MicroRNAsMirn155 microRNA, mouseNF-kappa BLDL receptor-related protein-1lipopolysaccharidemicroRNA-155NFκBtissue-type plasminogen activator

Identifiers

PMID26787872
PMCPMC4747752
OpenAlexW2265978074

What OpenQuestion holds

Textmetadata
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.