Open Access Research article

Expression and regulation of CCL18 in synovial fluid neutrophils of patients with rheumatoid arthritis

Judith Auer1, Markus Bläss2, Hendrik Schulze-Koops34, Stefan Russwurm25, Thomas Nagel3, Joachim R Kalden3, Martin Röllinghoff1 and Horst Ulrich Beuscher1*

Author Affiliations

1 Institute for Clinical Microbiology, Immunology and Hygiene, University of Erlangen-Nuremberg, Wasserturmstrasse 3-5, D-91054 Erlangen, Germany

2 SIRS-Lab GmbH, Winzerlaer Strasse 2, D-07745 Jena, Germany

3 Department of Internal Medicine III and Institute for Clinical Immunology, Rheumatology and Onkology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany

4 Nikolaus Fiebiger Centre for Molecular Medicine, Clinical Research Group III, University of Erlangen-Nuremberg, Glücksstrasse 5, D-91054 Erlangen, Germany

5 Clinics of Anesthesiology and Intensive Therapy, Friedrich-Schiller-University of Jena, Bachstrasse 18, D-07743 Jena, Germany

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Arthritis Research & Therapy 2007, 9:R94  doi:10.1186/ar2294

Published: 17 September 2007

Abstract

Rheumatoid arthritis (RA) is characterized by the recruitment of leukocytes and the accumulation of inflammatory mediators within the synovial compartment. Release of the chemokine CCL18 has been widely attributed to antigen-presenting cells, including macrophages and dendritic cells. This study investigates the production of CCL18 in polymorphonuclear neutrophils (PMN), the predominant cell type recruited into synovial fluid (SF). Microarray analysis, semiquantitative and quantitative reverse transcriptase polymerase chain reaction identified SF PMN from patients with RA as a novel source for CCL18 in diseased joints. Highly upregulated expression of other chemokine genes was observed for CCL3, CXCL8 and CXCL10, whereas CCL21 was downregulated. The chemokine receptor genes were differentially expressed, with upregulation of CXCR4, CCRL2 and CCR5 and downregulation of CXCR1 and CXCR2. In cell culture experiments, expression of CCL18 mRNA in blood PMN was induced by tumor necrosis factor α, whereas synthesis of CCL18 protein required additional stimulation with a combination of IL-10 and vitamin D3. In comparison, recruited SF PMN from patients with RA were sensitized for CCL18 production, because IL-10 alone was sufficient to induce CCL18 release. These results suggest a release of the T cell-attracting CCL18 by PMN when recruited to diseased joints. However, its production is tightly regulated at the levels of mRNA expression and protein synthesis.