Evidence map›Paper›PMID 24612997›Full record

ArticleArthritis research & therapy2014

Angiotensin receptor type 1 and endothelin receptor type A on immune cells mediate migration and the expression of IL-8 and CCL18 when stimulated by autoantibodies from systemic sclerosis patients.

Jeannine Günther, Angela Kill, Mike Oliver Becker, Harald Heidecke, Judith Rademacher, Elise Siegert, Mislav Radić, Gerd-Rüdiger Burmester, Duska Dragun, Gabriela Riemekasten

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Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 117 citations in OpenAlex.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

10 authors at 1 institution in 2 countries.

Jeannine Günther
Angela Kill
Mike Oliver Becker
Harald Heidecke
Judith Rademacher
Elise Siegert
Mislav Radić
Gerd-Rüdiger Burmester
Duska Dragun
Gabriela Riemekasten
Charité - Universitätsmedizin Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAgonistic autoantibodies (Aabs) against the angiotensin II receptor type 1 (AT1R) and the endothelin receptor type A (ETAR) have been identified in patients with systemic sclerosis (SSc). In our present study, we examined the expression of the AT1R and the ETAR in human immune cells and the pathological effects mediated through these receptors by their corresponding Aabs.

methodsProtein expression of AT1R and ETAR on peripheral blood mononuclear cells (PBMCs) from healthy individuals and SSc patients was analyzed using flow cytometry, and mRNA expression of both receptors in PBMCs from healthy donors was examined by real-time PCR. In addition, PBMCs from healthy donors were stimulated in vitro with affinity-purified immunoglobulin G (IgG) fractions from SSc patients positive for AT1R and ETAR Aabs, as well as with IgG from healthy donors serving as controls. Alterations in cell surface marker expression, cytokine secretion and chemotactic motility were analyzed using flow cytometry, enzyme-linked immunosorbent assays and chemotaxis assays, respectively. The results were correlated with the characteristics and clinical findings of the IgG donors.

resultsBoth AT1R and ETAR were expressed on PBMCs in humans. Protein expression of both receptors was decreased in SSc patients compared with that of healthy donors and declined during the course of disease. IgG fractions of SSc patients positive for AT1R and ETAR Aabs induced T-cell migration in an Aab level-dependent manner. Moreover, IgG of SSc patients stimulated PBMCs to produce more interleukin 8 (IL-8) and chemokine (C-C motif) ligand 18 (CCL18) than did the IgG of healthy donors. All effects were significantly reduced by selective AT1R and ETAR antagonists. Statistical analysis revealed an association of SSc-IgG induced high IL-8 concentrations with an early disease stage and of high CCL18 concentrations with lung fibrosis onset and vascular complications in the respective IgG donors.

conclusionIn our present study, we could demonstrate the expression of both AT1R and ETAR on human peripheral T cells, B cells and monocytes. The decreased receptor expression in SSc patients, the inflammatory and profibrotic effects upon Aab stimulation of PBMCs in vitro and the associations with clinical findings suggest a role for Aab-induced activation of immune cells mediated by the AT1R and the ETAR in the pathogenesis or even the onset of the disease.

Indexed as

Cell MovementAdultAutoantibodiesChemokines, CCChemotaxis, LeukocyteEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansInterleukin-18MaleMiddle AgedMonocytesReal-Time Polymerase Chain ReactionReceptor, Angiotensin, Type 1Receptor, Endothelin AAutoantibodiesCCL18 protein, humanChemokines, CCInterleukin-18Receptor, Angiotensin, Type 1Receptor, Endothelin A

Identifiers

PMID24612997
PMCPMC4060229
OpenAlexW2098824799

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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.