{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T14:30:05Z","timestamp":1773412205011,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008635","name":"University of Texas Health Science Center at San Antonio","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008635","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> It has been suggested that cyclosporine A (CsA) induces gingival enlargement by promoting an increase in the gingival extracellular matrix (ECM). Nonetheless, the variable occurrence of CsA\u2010induced gingival enlargement in patients receiving this medication indicates a multifactorial pathogenesis. Clinical observations suggest that local inflammation is associated with the development and severity of CsA\u2010induced gingival enlargement. Therefore, the purpose of this study is to investigate the effects of CsA and inflammation on the production of ECM homeostatic mediators.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The effects of CsA and inflammation (as assessed using interleukin [IL]\u20101\u03b2) on the secretion of mediators involved in ECM homeostasis were determined using fibroblast monolayers and three\u2010dimensional (3D) models of the human oral mucosa. Fibroblast monolayers and 3D cultures were treated with CsA alone or in combination with IL\u20101\u03b2 for up to 72 hours, and the secretion of matrix metalloproteinases (MMPs) 1, 2, 3, 8, 9, 10, and 13 and tissue inhibitors of MMPs (TIMPs) 1, 2, and 4 into the culture medium was assessed using enzyme\u2010linked immunoassay\u2013based antibody arrays.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Fibroblast monolayers responded to CsA with no changes in the secretion of ECM mediators. Conversely, 3D cultures responded to CsA treatment with a reduction in MMP\u201010 secretion. IL\u20101\u03b2 alone triggered higher secretory levels of MMPs in both fibroblast monolayers (MMP\u20103 and MMP\u201010) and 3D cultures (MMP\u20109 and MMP\u201010). Importantly, fibroblast monolayers and 3D cultures treated with a combination of IL\u20101\u03b2 and CsA showed a decrease in the MMP\u20101\/TIMP\u20101 ratio.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> These data support the hypothesis that inflammation may alter the pathogenesis of CsA\u2010induced gingival enlargement by promoting a synergistic decrease in the MMP\u20101\/TIMP\u20101 ratio.<\/jats:p>","DOI":"10.1902\/jop.2012.120224","type":"journal-article","created":{"date-parts":[[2012,8,30]],"date-time":"2012-08-30T17:39:08Z","timestamp":1346348348000},"page":"634-640","source":"Crossref","is-referenced-by-count":10,"title":["Matrix Metalloproteinases, Tissue Inhibitors of Matrix Metalloproteinases, and Inflammation in Cyclosporine A\u2013Induced Gingival Enlargement: A Pilot In Vitro Study Using a Three\u2010Dimensional Model of the Human Oral 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