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Fibroblast-like synoviocytes (FLS) are known to be central mediators of joint damage in inflammatory arthritides through the production of matrix metalloproteinases (MMPs) that degrade collagen and of cytokines and chemokines that mediate the recruitment and activation of leukocytes. In this study we show that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella abortus<\/jats:named-content>infects and replicates in human FLS (SW982 cell line)<jats:italic>in vitro<\/jats:italic>and that infection results in the production of MMP-2 and proinflammatory mediators (interleukin-6 [IL-6], IL-8, monocyte chemotactic protein 1 [MCP-1], and granulocyte-macrophage colony-stimulating factor [GM-CSF]). Culture supernatants from<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>-infected FLS induced the migration of monocytes and neutrophils<jats:italic>in vitro<\/jats:italic>and also induced these cells to secrete MMP-9 in a GM-CSF- and IL-6-dependent fashion, respectively. Reciprocally, culture supernatants from<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>-infected monocytes and neutrophils induced FLS to produce MMP-2 in a tumor necrosis factor alpha (TNF-\u03b1)-dependent fashion. The secretion of proinflammatory mediators and MMP-2 by FLS did not depend on bacterial viability, since it was also induced by heat-killed<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>(HKBA) and by a model<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>lipoprotein (L-Omp19). These responses were mediated by the recognition of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>antigens through Toll-like receptor 2. The intra-articular injection of HKBA or L-Omp19 into the knee joint of mice resulted in the local induction of the proinflammatory mediators MMP-2 and MMP-9 and in the generation of a mixed inflammatory infiltrate. These results suggest that FLS, and phagocytes recruited by them to the infection focus, may be involved in joint damage during brucellar arthritis through the production of MMPs and proinflammatory mediators.<\/jats:p>","DOI":"10.1128\/iai.05408-11","type":"journal-article","created":{"date-parts":[[2011,7,6]],"date-time":"2011-07-06T03:06:44Z","timestamp":1309921604000},"page":"3619-3632","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Potential Role of Fibroblast-Like Synoviocytes in Joint Damage Induced by Brucella abortus Infection through Production and Induction of Matrix Metalloproteinases"],"prefix":"10.1128","volume":"79","author":[{"given":"Romina","family":"Scian","sequence":"first","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Barrionuevo","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Laboratorio de Inmunogen\u00e9tica, Hospital de Cl\u00ednicas Jos\u00e9 de San Mart\u00edn, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo H.","family":"Giambartolomei","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Laboratorio de Inmunogen\u00e9tica, Hospital de Cl\u00ednicas Jos\u00e9 de San Mart\u00edn, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio A.","family":"De Simone","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Fisiolog\u00eda Animal, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia I.","family":"Vanzulli","sequence":"additional","affiliation":[{"name":"Academia Nacional de Medicina de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Fossati","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo C.","family":"Baldi","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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