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A<jats:italic>virB10<\/jats:italic>mutant of<jats:italic>B. abortus<\/jats:italic>could infect but not replicate within osteoblasts, suggesting a role for the type IV secretion system in intracellular survival. Infected osteoblasts produced low levels of chemokines (interleukin-8 [IL-8] and macrophage chemoattractant protein 1 [MCP-1]) and did not produce proinflammatory cytokines (IL-1\u03b2, IL-6, and tumor necrosis factor alpha [TNF-\u03b1]). However, osteoblasts stimulated with culture supernatants from<jats:italic>Brucella<\/jats:italic>-infected human monocytes (THP-1 cell line) produced chemokines at levels 12-fold (MCP-1) to 17-fold (IL-8) higher than those of infected osteoblasts and also produced IL-6. In the inverse experiment, culture supernatants from<jats:italic>Brucella<\/jats:italic>-infected osteoblasts induced the production of IL-8, IL-1\u03b2, IL-6, and TNF-\u03b1 by THP-1 cells. The induction of TNF-\u03b1 and IL-1\u03b2 was largely due to granulocyte-macrophage colony-stimulating factor produced by infected osteoblasts, as demonstrated by inhibition with a specific neutralizing antibody. This study shows that<jats:italic>Brucella<\/jats:italic>can invade and replicate within human osteoblastic cell lines, which can directly and indirectly mount a proinflammatory response. Both phenomena may have a role in the chronic inflammation and bone and joint destruction observed in osteoarticular brucellosis.<\/jats:p>","DOI":"10.1128\/iai.01259-08","type":"journal-article","created":{"date-parts":[[2008,12,23]],"date-time":"2008-12-23T01:45:28Z","timestamp":1229996728000},"page":"984-995","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection with<i>Brucella<\/i>spp"],"prefix":"10.1128","volume":"77","author":[{"given":"M. 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