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Rheumatology Advance Access published online on October 4, 2008
Rheumatology, doi:10.1093/rheumatology/ken383
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes

H. Brühl1, M. Mack2, M. Niedermeier2, D. Lochbaum1, J. Schölmerich1 and R. H. Straub1

1Department of Internal Medicine I and 2Department of Internal Medicine II, University Hospital, Regensburg, Germany

Correspondence to: Correspondence to: H. Brühl, Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany. E-mail: hilke.bruehl{at}klinik.uni-regensburg.de


  Abstract

Objectives. We have characterized the expression and the function of the chemokine receptor CCR7 on fibroblast-like synoviocytes (FLS) of patients with RA and OA and on dermal fibroblasts.

Methods. FLS were obtained after enzymatic digestion of synovial tissue (ST) of patients with RA and OA undergoing knee replacement surgery and taken into culture for chemokine receptor analysis by RT–PCR, flow cytometry and functional tests. Immunofluorescence for CCR7, fibroblast and T-cell markers was performed on ST of RA and OA patients. To study the response of FLS to CCR7 ligands and other chemokines, migration assays were performed in modified Boyden chambers. After stimulation of FLS with CCR7 ligands, the secretion of VEGF was evaluated by ELISA and Luminex.

Results. CCR7 is expressed on FLS of patients with RA and OA, but not on dermal fibroblasts. FLS migrated in response to the CCR7 ligands, CCL19 and CCL21. Stimulation of FLS with CCL19 resulted in a significantly increased secretion of VEGF of RA- and OA-FLS.

Conclusion. Apart from the migration of FLS in response to CCL19 and CCL21, it was shown that activation of the CCR7 receptor on FLS results in an enhanced VEGF secretion. A considerable expression of CCR7 ligands in proximity to perivascular infiltrates has previously been described in inflamed synovial tissue of RA patients. Stimulation of FLS via CCR7 could thereby contribute to angiogenesis in the synovial tissue.

KEY WORDS: Chemotactic factors, Cytokines and inflammation, Fibroblast, Inflammation, CCR7, Angiogenesis

Submitted 11 January 2008; revised version accepted 2 September 2008.
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