{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:28:37Z","timestamp":1760887717556},"reference-count":73,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,2,19]],"date-time":"2004-02-19T00:00:00Z","timestamp":1077148800000},"content-version":"vor","delay-in-days":4828,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[1990,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To investigate the mechanism of cyclosporine (Cs)\u2010induced fibrous gingival enlargement, the indirect effects of Cs on fibroblast collagenolysis via the drug's effect on the synthesis of the fibroblast regulatory monokines interleukin\u20101\u03b2 (IL\u20101\u03b2) and tumor necrosis factor\u2010\u03b1 (TNF\u03b1) have been studied. Peripheral blood monocytes stimulated with lipopolysaccharide (LPS) for 48 h produced conditioned media (MCM\u2010LPS) that contained 665 pg\/ml IL\u20101\u03b2 and 16 pg\/ml TNF\u03b1 and significantly (<jats:italic>P<\/jats:italic> &lt; 0.001) enhanced the collagenase activity of a fibroblast strain (GN 23) derived from a healthy individual with clinically normal gingiva. The concurrent addition of Cs (50, 100, or 150 ng\/ml) with LPS to the monocytes (MCM\u2010LPS\u2010Cs) significantly diminished their ability to enhance GN 23 collagenase activity in a dose\u2010dependent manner, with MCM\u2010LPS\u2010Cs (150 ng\/ml) causing the greatest effect. Cs also significantly inhibited IL\u20101\u03b2 and TNF\u03b1 production. Although the greatest inhibition of both cytokines was at 50 ng\/ml Cs, the corresponding MCM\u2010LPS\u2010Cs caused the <jats:italic>least<\/jats:italic> diminution (16%) of the collagenase stimulation caused by MCM\u2010LPS (no Cs). This suggested that factor(s) other than or in addition to IL\u20101\u03b2 and TNF\u03b1 might be responsible for the stimulation of GN 23 collagenase activity. MCM\u2010LPS depleted of IL\u20101\u03b2 by affinity chromatography retained its stimulatory effect on GN 23 collagenolysis, and human recombinant IL\u20101\u03b2 and TNF\u03b1, when tested alone or together at levels found in the stimulatory MCM\u2010LPS and MCM\u2010LPS\u2010Cs, did not stimulate GN 23 collagenase activity as did the crude conditioned media. This evidence suggested that the conditioned media contained the complex mixture of cytokines necessary to stimulate collagenase activity of this fibroblast strain and that IL\u20101\u03b2 and TNF\u03b1 were not necessarily involved. Cs may alter the synthesis of other collagenase\u2010stimulating cytokines, accounting for the diminished ability of Cs\u2010treated monocytes to enhance collagenase activity of susceptible fibroblast strains. Decreased collagenase activity, therefore, resulting from Cs suppression of monokine production, may be an important factor in the development of fibrous gingival enlargement seen in some susceptible patients treated with Cs.<\/jats:p>","DOI":"10.1002\/jcb.240440407","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T20:36:05Z","timestamp":1117312565000},"page":"253-264","source":"Crossref","is-referenced-by-count":38,"title":["Interleukin\u20101\u03b2\u2010 and tumor necrosis factor\u2010\u03b1\u2010independent monocyte stimulation of fibroblast collagenase activity"],"prefix":"10.1002","volume":"44","author":[{"given":"David A.","family":"Tipton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Pabst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa 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