{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:21:43Z","timestamp":1788618103211,"version":"build-2803163510"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The innate immune system plays an important role in rheumatoid arthritis (RA) pathogenesis. Previous studies support the role of TLR2 and 4 in RA and experimental arthritis models; however, the regulation and pathogenic effect of TLR5 is undefined in RA. In this study, we show that TLR5 is elevated in RA and osteoarthritis ST lining and sublining macrophages and endothelial cells compared with normal individuals. Furthermore, expression of TLR5 is elevated in RA synovial fluid macrophages and RA peripheral blood monocytes compared with RA and normal peripheral blood in vitro-differentiated macrophages. We also found that TLR5 on RA monocytes is an important modulator of TNF-\u03b1 in RA synovial fluid and that TLR5 expression on these cells strongly correlates with RA disease activity and TNF-\u03b1 levels. Interestingly, TNF-\u03b1 has a feedback regulation with TLR5 expression in RA monocytes, whereas expression of this receptor is regulated by IL-17 and IL-8 in RA macrophages and fibroblasts. We show that RA monocytes and macrophages are more responsive to TLR5 ligation compared with fibroblasts despite the proinflammatory response being mediated through the same signaling pathways in macrophages and fibroblasts. In conclusion, we document the potential role of TLR5 ligation in modulating transcription of TNF-\u03b1 from RA synovial fluid and the strong correlation of TLR5 and TNF-\u03b1 with each other and with disease activity score in RA monocytes. Our results suggest that expression of TLR5 may be a predictor for RA disease progression and that targeting TLR5 may suppress RA.<\/jats:p>","DOI":"10.4049\/jimmunol.1102977","type":"journal-article","created":{"date-parts":[[2012,6,2]],"date-time":"2012-06-02T05:23:17Z","timestamp":1338614597000},"page":"475-483","source":"Crossref","is-referenced-by-count":69,"title":["TLR5, a Novel and Unidentified Inflammatory Mediator in Rheumatoid Arthritis that Correlates with Disease Activity Score and Joint TNF-\u03b1 Levels"],"prefix":"10.1093","volume":"189","author":[{"given":"Nathan D","family":"Chamberlain","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga M","family":"Vila","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V","family":"Volin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Midwestern University, Chicago College of Osteopathic Medicine , Downers Grove, IL 60515"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suncica","family":"Volkov","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M","family":"Pope","sequence":"additional","affiliation":[{"name":"Department of Medicine, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Swedler","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Arthur M","family":"Mandelin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Shahrara","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,7,1]]},"reference":[{"key":"2025032409161341400_r1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cellimm.2005.04.018","article-title":"The role of Toll-like receptor signalling in the pathogenesis of arthritis","volume":"233","author":"Brentano","year":"2005","journal-title":"Cell. 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