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Patients with rheumatoid arthritis are more prone to <jats:italic>S. aureus<\/jats:italic>-mediated septic arthritis. Various types of collagen form the major structural matrix of different connective tissues of the body. These different collagens are degraded by specific matrix metalloproteinases (MMPs) produced by fibroblasts, other connective tissue cells, and inflammatory cells that are induced by interleukin-1 (IL-1) and tumor necrosis factor (TNF). To determine the host's contribution in the joint destruction of <jats:italic>S. aureus<\/jats:italic>-mediated septic arthritis, we analyzed the MMP expression profile in human dermal and synovial fibroblasts upon exposure to culture supernatant and whole cell lysates of <jats:italic>S. aureus<\/jats:italic>. Human dermal and synovial fibroblasts treated with cell lysate and filtered culture supernatants had significantly enhanced expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-10, and MMP-11 compared with the untreated controls (<jats:italic>p<\/jats:italic> &lt; 0.05). In the <jats:italic>S. aureus<\/jats:italic> culture supernatant, the MMP induction activity was identified to be within the molecular-weight range of 30 to &gt;50 kDa. The MMP expression profile was similar in fibroblasts exposed to a combination of IL-1\/TNF. mRNA levels of several genes of the mitogen-activated protein kinase (MAPK) signal transduction pathway were significantly elevated in fibroblasts treated with <jats:italic>S. aureus<\/jats:italic> cell lysate and culture supernatant. Also, tyrosine phosphorylation was significantly higher in fibroblasts treated with <jats:italic>S. aureus<\/jats:italic> components. Tyrosine phosphorylation and MAPK gene expression patterns were similar in fibroblasts treated with a combination of IL-1\/TNF and <jats:italic>S. aureus<\/jats:italic>. Mutants lacking staphylococcal accessory regulator (<jats:italic>Sar<\/jats:italic>) and accessory gene regulator (<jats:italic>Agr<\/jats:italic>), which cause significantly less severe septic arthritis in murine models, were able to induce expression of several MMP mRNA comparable with that of their isogenic parent strain but induced notably higher levels of tissue inhibitors of metalloproteinases (TIMPs). To our knowledge, this is the first report of induction of multiple MMP\/TIMP expression from human dermal and synovial fibroblasts upon <jats:italic>S. aureus<\/jats:italic> treatment. We propose that host-derived MMPs contribute to the progressive joint destruction observed in <jats:italic>S. aureus<\/jats:italic>-mediated septic arthritis.<\/jats:p>","DOI":"10.1186\/ar2086","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T07:34:39Z","timestamp":1164699279000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts by Staphylococcus aureus: implications in the pathogenesis of septic arthritis and other soft tissue infections"],"prefix":"10.1186","volume":"8","author":[{"given":"Siva","family":"Kanangat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Postlethwaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Hasty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Smeltzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney","family":"Appling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Schaberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,11,27]]},"reference":[{"key":"1951_CR1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1600-0765.1999.tb02271.x","volume":"34","author":"E Josefsson","year":"1999","unstructured":"Josefsson E, Tarkowski A: Staphylococcus aureus -induced inflammation and bone destruction in experimental models of septic arthritis. 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