Monocytic Angiotensin and Endothelin Receptor Imbalance Modulate Secretion of the Profibrotic Chemokine Ligand 18

Judith Rademacher; Angela Kill; Kathrin Mattat; Duska Dragun; Elise Siegert; Jeannine Günther; Gabriela Riemekasten

doi:10.3899/jrheum.150474

Monocytic Angiotensin and Endothelin Receptor Imbalance Modulate Secretion of the Profibrotic Chemokine Ligand 18

J Rheumatol. 2016 Mar;43(3):587-91. doi: 10.3899/jrheum.150474. Epub 2016 Jan 15.

Authors

Judith Rademacher¹, Angela Kill¹, Kathrin Mattat¹, Duska Dragun¹, Elise Siegert¹, Jeannine Günther¹, Gabriela Riemekasten²

Affiliations

¹ From the Department of Rheumatology and Clinical Immunology, and the Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; Cell Autoimmunity, German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin; Department of Rheumatology, University of Lübeck, Lübeck, Germany.J. Rademacher, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; A. Kill, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; K. Mattat, Department of Rheumatology and Clinical Immunology, Charité University Hospital; D. Dragun, Professor, Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; E. Siegert, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital; J. Günther*, MSc, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; G. Riemekasten*, Professor, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ, and Department of Rheumatology, University of Lübeck.
² From the Department of Rheumatology and Clinical Immunology, and the Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; Cell Autoimmunity, German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin; Department of Rheumatology, University of Lübeck, Lübeck, Germany.J. Rademacher, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; A. Kill, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; K. Mattat, Department of Rheumatology and Clinical Immunology, Charité University Hospital; D. Dragun, Professor, Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; E. Siegert, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital; J. Günther*, MSc, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; G. Riemekasten*, Professor, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ, and Department of Rheumatology, University of Lübeck. Gabriela.Riemekasten@uksh.de.

PMID: 26773103
DOI: 10.3899/jrheum.150474

Abstract

Objective: To assess monocytic expression and ratio of angiotensin and endothelin receptors in systemic sclerosis (SSc) and their functional relevance.

Methods: Receptor expression was measured by flow cytometry. Chemokine ligand 18 (CCL18) concentration in supernatants of peripheral blood mononuclear cells stimulated with immunoglobulin G was measured by ELISA.

Results: Monocytes of patients with SSc presented an increased angiotensin II Type 1 receptor (AT1R)/AT2R ratio compared with those of healthy donors. Patients with lung fibrosis and patients with high modified Rodnan skin score showed a reduced endothelin 1 Type A receptor (ETAR)/ETBR ratio. High AT1R/AT2R, but low ETAR/ETBR ratios corresponded to higher CCL18 secretion.

Conclusion: Altered angiotensin and endothelin receptor ratios observed in SSc influence autoantibody-mediated effects such as secretion of profibrotic CCL18.

Keywords: ANGIOTENSIN RECEPTORS; AUTOANTIBODIES; ENDOTHELIN RECEPTORS; HUMAN CCL18 PROTEIN; MONOCYTES; SYSTEMIC SCLERODERMA.

MeSH terms

Adult
Aged
Chemokines, CC / blood*
Female
Humans
Leukocytes, Mononuclear / metabolism
Male
Middle Aged
Monocytes / metabolism*
Receptor, Angiotensin, Type 1 / metabolism*
Receptor, Endothelin A / metabolism*
Scleroderma, Systemic / metabolism*
Young Adult

Substances

CCL18 protein, human
Chemokines, CC
Receptor, Angiotensin, Type 1
Receptor, Endothelin A