Dr. Mandelin has received fees for serving on the speakers' bureaus of Abbott and UCB (less than $10,000 each).
Characterization of CCL19 and CCL21 in rheumatoid arthritis
Article first published online: 30 MAR 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 4, pages 914–922, April 2011
How to Cite
Pickens, S. R., Chamberlain, N. D., Volin, M. V., Pope, R. M., Mandelin, A. M. and Shahrara, S. (2011), Characterization of CCL19 and CCL21 in rheumatoid arthritis. Arthritis & Rheumatism, 63: 914–922. doi: 10.1002/art.30232
- Issue published online: 3 MAR 2011
- Article first published online: 30 MAR 2011
- Accepted manuscript online: 10 JAN 2011 11:32AM EST
- Manuscript Accepted: 28 DEC 2010
- Manuscript Received: 8 JUN 2010
- NIH. Grant Numbers: AR-056099, AR-055240
- Arthritis National Research Foundation
- Within Our Reach program of the American College of Rheumatology Research and Education Foundation
- US Department of Defense. Grant Number: award PR-093477
To characterize the expression of CCL19 and CCL21 in rheumatoid arthritis (RA) synovial tissue (ST) and to examine their regulation and pathogenetic role in macrophages and RA ST fibroblasts.
Expression of CCL19 and CCL21 in RA and normal ST was demonstrated by immunohistochemistry analysis. CCL19 and CCL21 levels in synovial fluid (SF) from patients with osteoarthritis (OA), juvenile idiopathic arthritis, psoriatic arthritis (PsA), and RA were quantified by enzyme-linked immunosorbent assay (ELISA). Regulation of CCL19 and CCL21 expression in in vitro–differentiated RA peripheral blood macrophages as well as RA ST fibroblasts was determined by real-time reverse transcription–polymerase chain reaction. Proangiogenic factor production in CCL19- and CCL21-activated in vitro–differentiated peripheral blood macrophages and RA ST fibroblasts was examined by ELISA.
CCL19 and CCL21 were elevated in RA ST compared to tissue from normal controls. Levels of CCL19 and CCL21 were greatly increased in RA and PsA SF versus OA SF. In RA macrophages and fibroblasts, expression of CCL19 was increased by stimulation with lipopolysaccharide, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β). However, CCL21 expression was modulated only by IL-1β in RA fibroblasts, and by TNFα and RA SF in RA macrophages. CCL19 and CCL21 activation induced vascular endothelial growth factor and angiotensin I (Ang I) production in RA ST fibroblasts and secretion of IL-8 and Ang I from macrophages.
The findings of the present study identify, for the first time, regulators of CCL19 and CCL21 in RA fibroblasts and in vitro–differentiated RA peripheral blood macrophages and demonstrate a novel role of CCL19/CCL21 in angiogenesis in RA.