{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:55:34Z","timestamp":1789811734630,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,3,30]],"date-time":"2011-03-30T00:00:00Z","timestamp":1301443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010linked immunosorbent assay (ELISA). Regulation of CCL19 and CCL21 expression in in vitro\u2013differentiated RA peripheral blood macrophages as well as RA ST fibroblasts was determined by real\u2010time reverse transcription\u2013polymerase chain reaction. Proangiogenic factor production in CCL19\u2010 and CCL21\u2010activated in vitro\u2013differentiated peripheral blood macrophages and RA ST fibroblasts was examined by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 \u03b1 (TNF\u03b1), and interleukin\u20101\u03b2 (IL\u20101\u03b2). However, CCL21 expression was modulated only by IL\u20101\u03b2 in RA fibroblasts, and by TNF\u03b1 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\u20108 and Ang I from macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings of the present study identify, for the first time, regulators of CCL19 and CCL21 in RA fibroblasts and in vitro\u2013differentiated RA peripheral blood macrophages and demonstrate a novel role of CCL19\/CCL21 in angiogenesis in RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30232","type":"journal-article","created":{"date-parts":[[2011,1,10]],"date-time":"2011-01-10T16:42:19Z","timestamp":1294677739000},"page":"914-922","source":"Crossref","is-referenced-by-count":124,"title":["Characterization of CCL19 and CCL21 in rheumatoid arthritis"],"prefix":"10.1002","volume":"63","author":[{"given":"Sarah R.","family":"Pickens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan D.","family":"Chamberlain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Volin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Pope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Arthur M.","family":"Mandelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Shahrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,30]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0647"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2009.02.002"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2297"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1513"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-11-4353"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken383"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2009.03.021"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838906"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.02.010"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0800729"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511043103"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000255581.38523.7c"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22939"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200107)44:7<1568::AID-ART280>3.0.CO;2-1"},{"key":"e_1_2_7_16_2","first-page":"244","article-title":"4A11, a monoclonal antibody recognizing a novel antigen expressed on aberrant vascular endothelium: upregulation in an in vivo model of contact dermatitis","volume":"144","author":"Koch AE","year":"1994","journal-title":"Am J Pathol"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21033"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.3447"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar407"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2477"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802246"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901942"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903271"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.5333"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-005-0044-5"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.08.269"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2007.01933.x"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00206.x"},{"key":"e_1_2_7_29_2","first-page":"2209","article-title":"Endotoxin upregulates CCR7 and its ligands in the lymphatic\u2010free mouse iris","volume":"13","author":"Mackensen F","year":"2007","journal-title":"Mol Vis"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0807567"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710038200"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1222"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.8.4.7332"}],"container-title":["Arthritis &amp; 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