Evidence map›Paper›PMID 29268771›Full record

ArticleJournal of neuroinflammation2017

Monocyte-derived tissue transglutaminase in multiple sclerosis patients: reflecting an anti-inflammatory status and function of the cells?

Claudia Sestito, John J P Brevé, Marja C J A van Eggermond, Joep Killestein, Charlotte E Teunissen, Joram van Rossum, Micha M M Wilhelmus, Benjamin Drukarch, Peter J van den Elsen, Anne-Marie van Dam

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

8 citing papers in PubMed, 15 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

10 authors at 3 institutions in 1 country.

Claudia SestitoDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Postbus 7057, 1007 MB, Amsterdam, the Netherlands.
John J P BrevéDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Postbus 7057, 1007 MB, Amsterdam, the Netherlands.
Marja C J A van EggermondDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Joep KillesteinDepartment of Neurology, VU University Medical Center, Amsterdam, the Netherlands.
Charlotte E TeunissenDepartment of Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands.
Joram van RossumDepartment of Neurology, VU University Medical Center, Amsterdam, the Netherlands.
Micha M M WilhelmusDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Postbus 7057, 1007 MB, Amsterdam, the Netherlands.
Benjamin DrukarchDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Postbus 7057, 1007 MB, Amsterdam, the Netherlands.
Peter J van den ElsenDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Anne-Marie van DamDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Postbus 7057, 1007 MB, Amsterdam, the Netherlands. amw.vandam@vumc.nl.
Amsterdam Neuroscience · NLAmsterdam UMC Location VUmc · NLLeiden University Medical Center · NL

Funding

European Union Framework Programme 7 Marie Curie TRANSPATH ITN 289964Stichting MS Research 10-701MSStichting MS Research 14-865MS
6 · The paper itself

Abstract

backgroundLeukocyte infiltration into the central nervous system is an important feature of multiple sclerosis (MS) pathology. Among the infiltrating cells, monocytes comprise the largest population and are considered to play a dual role in the course of the disease. The enzyme tissue transglutaminase (TG2), produced by monocytes, plays a central role in monocyte adhesion/migration in animal models of MS. In the present study, we questioned whether TG2 expression is altered in monocytes from MS patients compared to healthy control (HC) subjects. Moreover, we determined the inflammatory status of these TG2-expressing monocytes, what inflammatory factor regulates TG2 expression, and whether TG2 can functionally contribute to their adhesion/migration processes.

methodsPrimary human monocytes from MS patients and HC subjects were collected, RNA isolated and subjected to qPCR analysis. Human THP-1 monocytes were lentivirally transduced with TG2 siRNA or control and treated with various cytokines. Subsequently, mRNA levels of inflammatory factors, adhesion properties, and activity of RhoA were analyzed in interleukin (IL)-4-treated monocytes.

resultsTG2 mRNA levels are significantly increased in monocytes derived from MS patients compared to HC subjects. In addition, correlation analyses indicated that TG2-expressing cells display a more anti-inflammatory, migratory profile in MS patients. Using THP-1 monocytes, we observed that IL-4 is a major trigger of TG2 expression in these cells. Furthermore, knockdown of TG2 expression leads to a pro-inflammatory profile and reduced adhesion/migration properties of IL-4-treated monocytes.

conclusionsTG2-expressing monocytes in MS patients have a more anti-inflammatory profile. Furthermore, TG2 mediates IL-4-induced anti-inflammatory status in THP-1 monocytes, adhesion, and cytoskeletal rearrangement in vitro. We thus propose that IL-4 upregulates TG2 expression in monocytes of MS patients, driving them into an anti-inflammatory status.

Indexed as

AdultAgedCell AdhesionCell DifferentiationFemaleGTP-Binding ProteinsHumansInflammationMaleMiddle AgedMonocytesMultiple SclerosisProtein Glutamine gamma Glutamyltransferase 2TransglutaminasesYoung AdultGTP-Binding ProteinsProtein Glutamine gamma Glutamyltransferase 2TransglutaminasesAdhesion/migrationCytokineHuman monocytesInflammationMultiple sclerosisTissue transglutaminase

Identifiers

PMID29268771
PMCPMC5740592
OpenAlexW2781059885

What OpenQuestion holds

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LicenceCC BY
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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.