Evidence map›Paper›PMID 28522438›Full record

ArticleCirculation research2017

Anti-Inflammatory Effects of OxPAPC Involve Endothelial Cell-Mediated Generation of LXA4.

Yunbo Ke, Noureddine Zebda, Olga Oskolkova, Taras Afonyushkin, Evgeny Berdyshev, Yufeng Tian, Fanyong Meng, Nicolene Sarich, Valery N Bochkov, Ji Ming Wang and 2 more

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In one paragraph

Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

25 citing papers in PubMed, 43 citations in OpenAlex.

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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

12 authors at 3 institutions in 1 country.

Yunbo KeFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Noureddine ZebdaFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Olga OskolkovaFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Taras AfonyushkinFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Evgeny BerdyshevFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Yufeng TianFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Fanyong MengFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Nicolene SarichFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Valery N BochkovFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Ji Ming WangFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Anna A BirukovaFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.).
Konstantin G BirukovFrom the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Pharmaceutical Sciences, University of Graz, Austria (V.N.B.). kbirukov@anes.umm.edu.
National Jewish Health · USNational Cancer Institute · USUniversity of Colorado Denver · US

Funding

Control of Lung Permeability by Oxidized PhospholipidsR01HL076259 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOV, KONSTANTIN · 2004 to 2023
$6.8M
Molecular control of lung endothelial barrier function in ALIR01HL087823 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOV, KONSTANTIN · 2008 to 2020
$4.6M
Microtubule-associated regulation of acute lung injuryR01HL107920 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOVA, ANNA · 2011 to 2019
$2.8M
Differential mechano-signaling in vascular endothelium by varying degrees of mechanical stretch - Resubmission 01R01HL130431 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOVA, ANNA · 2016 to 2019
$1.6M
Microtubule control of septic inflammationR01GM114171 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOVA, ANNA · 2015 to 2018
$1.2M
Microtubule-associated regulation of acute lung injuryR56HL107920 · NHLBI · UNIVERSITY OF CHICAGO · PI BIRUKOVA, ANNA · 2015 to 2015
$395k
NHLBI NIH HHS R01 HL076259NHLBI NIH HHS R01 HL087823NHLBI NIH HHS R01 HL107920NHLBI NIH HHS R01 HL130431NHLBI NIH HHS R56 HL107920NIGMS NIH HHS R01 GM114171
6 · The paper itself

Abstract

rationaleOxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) generates a group of bioactive oxidized phospholipid products with a broad range of biological activities. Barrier-enhancing and anti-inflammatory effects of OxPAPC on pulmonary endothelial cells are critical for prevention of acute lung injury caused by bacterial pathogens or excessive mechanical ventilation. Anti-inflammatory properties of OxPAPC are associated with its antagonistic effects on Toll-like receptors and suppression of RhoA GTPase signaling.

objectiveBecause OxPAPC exhibits long-lasting anti-inflammatory and lung-protective effects even after single administration in vivo, we tested the hypothesis that these effects may be mediated by additional mechanisms, such as OxPAPC-dependent production of anti-inflammatory and proresolving lipid mediator, lipoxin A4 (LXA4). METHODS AND

resultsMass spectrometry and ELISA assays detected significant accumulation of LXA4 in the lungs of OxPAPC-treated mice and in conditioned medium of OxPAPC-exposed pulmonary endothelial cells. Administration of LXA4 reproduced anti-inflammatory effect of OxPAPC against tumor necrosis factor-α in vitro and in the animal model of lipopolysaccharide-induced lung injury. The potent barrier-protective and anti-inflammatory effects of OxPAPC against tumor necrosis factor-α and lipopolysaccharide challenge were suppressed in human pulmonary endothelial cells with small interfering RNA-induced knockdown of LXA4 formyl peptide receptor-2 (FPR2/ALX) and in mFPR2

conclusionsThis is the first demonstration that inflammation- and injury-associated phospholipid oxidation triggers production of anti-inflammatory and proresolution molecules, such as LXA4. This lipid mediator switch represents a novel mechanism of OxPAPC-assisted recovery of inflamed lung endothelium.

Indexed as

Acute Lung InjuryAnimalsAnti-Inflammatory Agents, Non-SteroidalCells, CulturedEndothelial CellsHumansLipoxinsMiceMice, Inbred C57BLMice, KnockoutPhosphatidylcholinesTreatment OutcomeAnti-Inflammatory Agents, Non-Steroidallipoxin A4Lipoxinsoxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholinePhosphatidylcholinesendothelial cellsinflammationlipoxinslung injuryphospholipidspulmonary circulation

Identifiers

PMID28522438
PMCPMC5886749
OpenAlexW2614730280

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Registered trials

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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.