{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:10:53Z","timestamp":1790835053829,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,2,28]],"date-time":"2003-02-28T00:00:00Z","timestamp":1046390400000},"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":[[2003,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To test the hypothesis that bacterial products acting as adjuvants, such as CpG oligodeoxynucleotides (ODNs) and peptidoglycans (PGs), are able to activate synoviocytes, and to determine the involvement of Toll\u2010like receptors (TLRs) in this activation process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cultured synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) were stimulated with CpG ODNs or PGs. The expression of various integrins was determined by fluorescence\u2010activated cell sorting. TLR and matrix metalloproteinase (MMP) messenger RNA (mRNA) was measured by real\u2010time polymerase chain reaction. Additionally, levels of interleukin\u20106 (IL\u20106) and IL\u20108 in the culture supernatants were assessed by enzyme\u2010linked immunosorbent assay. Blocking experiments were performed by adding anti\u2013TLR\u20102 and anti\u2013TLR\u20104 monoclonal antibodies to cultures stimulated with bacterial PGs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Incubation of synovial fibroblasts with CpG ODNs resulted in neither up\u2010regulation of the expression of integrins on the cell surface, up\u2010regulation of MMP mRNA expression, nor IL\u20106 and IL\u20108 production. However, incubation of RA synovial fibroblasts as well as OA synovial fibroblasts with staphylococcal PGs led to an up\u2010regulation of CD54 (ICAM\u20101) surface expression and to increased expression of MMP\u20101, MMP\u20103, and MMP\u201013 mRNA. Furthermore, production of the proinflammatory cytokines IL\u20106 and IL\u20108 was increased by treatment with PGs. We demonstrated that cultured synovial fibroblasts express low levels of TLR\u20102 and TLR\u20109 mRNA. TLR\u20102 was up\u2010regulated after stimulation with PGs, whereas TLR\u20109 mRNA remained at baseline levels after stimulation with CpG ODNs. Anti\u2013TLR\u20102 monoclonal antibodies significantly inhibited production of IL\u20106 and IL\u20108 induced by stimulation with PGs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrate that bacterial PGs activate synovial fibroblasts, at least partially via TLR\u20102, to express integrins, MMPs, and proinflammatory cytokines. Inhibition of TLR signaling pathways might therefore have a beneficial effect on both joint inflammation and joint destruction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10848","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T22:50:19Z","timestamp":1048027819000},"page":"642-650","source":"Crossref","is-referenced-by-count":156,"title":["Bacterial peptidoglycans but not CpG oligodeoxynucleotides activate synovial fibroblasts by toll\u2010like receptor signaling"],"prefix":"10.1002","volume":"48","author":[{"given":"Diego","family":"Kyburz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Rethage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhart","family":"Seibl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Lauener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate E.","family":"Gay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A.","family":"Carson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Gay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,2,28]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81109-5"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/41131"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35047123"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.17406"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.1.1"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80119-3"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200003)43:3<593::AID-ANR16>3.0.CO;2-1"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/9554"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar330"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.9.4340-4345.1999"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.2.944"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9305"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.6.863"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.8.5000"},{"key":"e_1_2_5_17_2","first-page":"955","article-title":"Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. 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