{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:18:35Z","timestamp":1762100315712,"version":"build-2065373602"},"reference-count":0,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[1999,12,1]],"date-time":"1999-12-01T00:00:00Z","timestamp":944006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[1999,12]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Cyclosporine A (CsA) is a widely used immunosuppressant, with clinical applications ranging from organ transplants to chronic inflammatory diseases. One of the side effects associated with CsA treatment is the development of gingival overgrowth. Exuberant growth of connective tissue within the periodontium can result from hyperactivity of resident fibroblasts. Fibroblasts are capable of secreting interleukin\u20106 (IL\u20106), which has been shown to enhance proliferation as well as collagen and glycosaminoglycan synthesis by these cells. We tested the hypothesis that one of the pathogenetic mechanisms underlying CsA\u2010induced fibrosis is an enhanced IL\u20106 secretion by gingival fibroblasts (GF) in response to this drug.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The ability of CsA to upregulate GF IL\u20106 secretion alone or in combination with bacterial challenge or other inflammatory cytokines was tested in an in vitro system. Fibroblast cultures were established from systemically healthy gingival tissue donors and were challenged with CsA in the absence or presence of bacteria, IL\u20101\u03b2, or tumor necrosis factor (TNF) \u03b1 as co\u2010stimulants. Nifedipine and phenytoin were also tested to further support findings with CsA. After 72 hours of incubation, culture supernatants were collected and analyzed for IL\u20106 content by ELISA.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We have shown that GF respond to CsA with an increase in IL\u20106 secretion. The magnitude of this response varies among cultures derived from different tissue donors. We have also demonstrated that GF IL\u20106 responses to bacterial challenge or TNF\u03b1 are downregulated by CsA. However, CsA synergizes with IL\u20101\u03b2 to further upregulate IL\u20106 secretion, and this effect is shared by phenytoin and nifedipine.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> We conclude that one of the pathogenetic mechanisms underlying drug\u2010induced gingival overgrowth may be enhanced secretion of IL\u20106 by GF in response to these medications. This is the first report on direct and indirect effects of gingival overgrowth\u2010related medications on GF IL\u20106 metabolism. This work will lay the foundation for future studies directed towards the development of prevention or treatment modalities for gingival overgrowth based on blocking the fibrogenic activities of IL\u20106 at the cellular level. <jats:italic>J Periodontol 1999;70:1464\u20101471.<\/jats:italic><\/jats:p>","DOI":"10.1902\/jop.1999.70.12.1464","type":"journal-article","created":{"date-parts":[[2005,2,2]],"date-time":"2005-02-02T06:03:52Z","timestamp":1107324232000},"page":"1464-1471","source":"Crossref","is-referenced-by-count":44,"title":["Regulation of Gingival Fibroblast Interleukin\u20106 Secretion by Cyclosporine A"],"prefix":"10.1002","volume":"70","author":[{"given":"Rakhi Sinha","family":"Morton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna I.","family":"Dongari\u2010Bagtzoglou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1999,12]]},"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.1999.70.12.1464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T10:32:47Z","timestamp":1760869967000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.1999.70.12.1464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12]]},"references-count":0,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1999,12]]}},"alternative-id":["10.1902\/jop.1999.70.12.1464"],"URL":"https:\/\/doi.org\/10.1902\/jop.1999.70.12.1464","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"type":"print","value":"0022-3492"},{"type":"electronic","value":"1943-3670"}],"subject":[],"published":{"date-parts":[[1999,12]]}}}