Fibroblast heterogeneity in collagenolytic response to cyclosporine

David Tipton, George P. Stricklin, Mustafa Kh Dabbous

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Abstract

To investigate the mechanism of cyclosporine (CS)‐induced fibrotic gingival enlargement, the effect of CS on the collagenolytic activities of 14 different human gingival fibroblast strains derived from healthy individuals with non‐inflammed gingiva was examined in vitro. There was marked heterogeneity among individuals in basal levels of collagenase activity, and there was also variation among the subpopulations derived from one strain. Fibroblasts from different individuals also varied markedly in their collagenolytic response to CS (0.1 to 0.75 μg/ml). In most strains, CS decreased collagenase activity, but in some, the drug caused no change or significantly increased activities. In most of the subpopulations CS significantly decreased collagenolytic activity. Two of the fibroblast strains and the subpopulations described above were examined for the production of immunoreactive collagenase and tissue inhibitor of metalloproteinase (TIMP). The two strains made similar amounts of collagenase, but differed markedly in TIMP levels; CS affected their collagenase production differently but had similar effects on TIMP. Among the subpopulations there was variation in the production of collagenase, although none made detectable levels of TIMP; they also varied in the production of both proteins in response to CS. In two of the subpopulations and in both strains at some concentrations, the effect of CS on the relative levels of collagenase and TIMP could account for the decreased collagenase activity; i.e., the level of collagenase was unchanged or decreased, and TIMP production was unchanged or increased. This study demonstrates the variation among individuals as well as intrastrain heterogeneity of human gingival fibroblasts with regard to collagenase activity and the production of collagenase and TIMP. The heterogeneity of the collagenolytic response of different gingival fibroblast strains and their subpopulations to CS treatment may partly explain the susceptibility of only some individuals to CS‐induced gingival enlargement.

Original languageEnglish (US)
Pages (from-to)152-165
Number of pages14
JournalJournal of Cellular Biochemistry
Volume46
Issue number2
DOIs
StatePublished - Jan 1 1991

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Collagenases
Fibroblasts
Tissue Inhibitor of Metalloproteinases
Cyclosporine
Matrix Metalloproteinase Inhibitors
Gingiva

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fibroblast heterogeneity in collagenolytic response to cyclosporine. / Tipton, David; Stricklin, George P.; Dabbous, Mustafa Kh.

In: Journal of Cellular Biochemistry, Vol. 46, No. 2, 01.01.1991, p. 152-165.

Research output: Contribution to journalArticle

Tipton, David ; Stricklin, George P. ; Dabbous, Mustafa Kh. / Fibroblast heterogeneity in collagenolytic response to cyclosporine. In: Journal of Cellular Biochemistry. 1991 ; Vol. 46, No. 2. pp. 152-165.
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