{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:02:51Z","timestamp":1761487371187},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T00:00:00Z","timestamp":1112832000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Protease\u2010activated receptor 1 (PAR\u20101) is the cell surface receptor for thrombin. It is unclear whether thrombin contributes to inflammation other than by effects on coagulation. We investigated the proinflammatory participation of PAR\u20101 in antigen\u2010induced arthritis (AIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Arthritis was induced by intraarticular injection of methylated bovine serum albumin (mBSA) in preimmunized PAR\u20101\u2013deficient (PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type (WT) mice. The disease was assessed after 7 days by histologic examination of knee joints after decalcification and Safranin O\/toluidine blue staining. Serum levels of anti\u2010mBSA IgG, interferon\u2010\u03b3, and interleukin\u20104 (IL\u20104) were determined by enzyme\u2010linked immunosorbent assay. T cell proliferation response was determined by measuring the incorporation of <jats:sup>3<\/jats:sup>H\u2010thymidine. Cytokine messenger RNA (mRNA) expression was detected in synovial tissues and peritoneal cells by real\u2010time polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Arthritis severity was significantly reduced in PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared with WT mice (<jats:italic>P<\/jats:italic> = 0.017). Analysis of individual aspects of joint histology revealed significant reductions in synovial exudates (<jats:italic>P<\/jats:italic> &lt; 0.001), cartilage degradation (<jats:italic>P<\/jats:italic> &lt; 0.01), and bone damage (<jats:italic>P<\/jats:italic> = 0.05) in PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Synovial IL\u20101, IL\u20106, and matrix metalloproteinase 13 (MMP\u201013) mRNA was significantly reduced in PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> mice. The titers of antigen\u2010specific serum anti\u2010mBSA total IgG, IgG1, and IgG2a were significantly reduced, and serum IL\u20104 was significantly increased in arthritic PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In contrast, no difference was observed in antigen\u2010induced T cell proliferation between PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> and WT mice. In vitro, thrombin\u2010induced (but not lipopolysaccharide\u2010induced) IL\u20101, IL\u20106, and MMP\u201013 mRNA expression was significantly impaired in PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared with WT controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data demonstrate the requirement of PAR\u20101 for the expression of AIA, the development of an antigen\u2010specific Ig response, thrombin\u2010induced macrophage cytokine and MMP expression, and the inhibitory effect of PAR\u20101 on serum IL\u20104. We conclude that PAR\u20101 plays a significant role in this model of arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21001","type":"journal-article","created":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T15:23:02Z","timestamp":1112887382000},"page":"1325-1332","source":"Crossref","is-referenced-by-count":44,"title":["Reduction of arthritis severity in protease\u2010activated receptor\u2013deficient mice"],"prefix":"10.1002","volume":"52","author":[{"given":"Yuan H.","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pam","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher B.","family":"Little","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda 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