Cyclosporin A effects on matrix gene products in gingival fibroblasts
Date
1995
DOI
Authors
Kabalan, Adriana
Version
OA Version
Citation
Abstract
Cyclosporin A (CsA) caused hypertrophy and fibrosis in gingiva and other tissues. Increased collagen synthesis and increased lysyl oxidase (LO.) activity have been previously found in lung and liver fibrosis In this study, the effect of pharmacologically relevant concentrations of CsA on LO. enzyme activity and steady state mRNA tevels in normal human gingival fibroblasts (NHGF) was measured. The steady state mRNA levels of coltagen and etastin in these cultures was also measured. Passage five fibroblastic cells obtained from clinically normal human gingiva were grown to confluence in DMEM containing 10% NBS, and were then cultured in DMEM containing 0.5% NBS for 36 hours. The cells were then treated with CsA or vehicle, and the cells were harvested at different time points (4, 12, 24 and 48 hours). Lysyl oxidase activity, ceU number, cell layer protein were assayed. RNA was isolated and analyzed by Northern blotting. We have found that normalized LO. activity increased by two fold in response to 1 x 10-99/ml to 1 x 10-6 g/ml CsA, but did not change consistently at concentrations above or below this range. Steady state levels of elastin mRNA did not change significantly in response to CsA treatment. LO. and a - 1 type I collagen mRNA levels were both found to increase by 2 fold in response to CsA treatment. CsA appears to alter the balance of synthesis of collagen and elastin; LO. activity and mRNA values are increased. An increase in the ratio of collagen to elastin synthesis coupled with increased crosslinking are consistent with the characteristics of fibrosis documented in other tissues. Early passage NHGF cells may provide a convenient cell culture model to study drug-induced gingival fibrosis.
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Thesis (M.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1995 (Periodontology and Oral Biology).
Includes bibliographical references: (leaves 50-59).
Thesis (M.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1995 (Periodontology and Oral Biology).
Includes bibliographical references: (leaves 50-59).
License
This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.