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Extracellular glycosaminoglycan changes in healthy and overgrown gingiva fibroblasts after cyclosporin A and cytokine treatments
Author(s) -
Stabellini G.,
Calastrini C.,
Mariani G.,
Gioia M.,
Caramelli E.,
Gagliano N.,
Dellavia C.,
Moscheni C.,
Vizzotto L.,
Calvi E. M.
Publication year - 2004
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2004.00217.x
Subject(s) - glycosaminoglycan , extracellular matrix , fibroblast , cytokine , transforming growth factor , extracellular , microbiology and biotechnology , chemistry , population , biology , immunology , cell culture , biochemistry , medicine , genetics , environmental health
Background: It has been demonstrated that cyclosporin A (CyA) blocks the immune system, acts on cytoskeleton and stimulates the production of extracellular matrix (ECM) and transforming growth factor‐β 1 (TGF‐ β 1 ). This cytokine, such as transforming growth factor‐α (TGF‐ α ), induces deposition of glycosaminoglycans (GAG), proteoglycans and collagen fibres in the ECM. Methods: In this work, we examined the effect induced by CyA, TGF‐ β 1 and TGF‐ α on cultures of healthy and overgrown human gingival fibroblasts in order to evaluate the glycosaminoglycan, cytoskeletal changes and the behaviour of fibroblasts after concanavalin A (Con A) treatment. Moreover, we examined gingival biopsies by Alcian blue histochemical staining and electron transmission microscopy. Results: Total and extracellular sulphated GAG in overgrown gingiva specimens and in derived fibroblast cultures treated with CyA and cytokines were significantly higher than controls. The action of cytokines was increased ( P ≤ 0.01) compared with CyA with a greater effect of TGF‐ α in comparison with TGF‐ β 1 ; the electron microscopy showed ECM accumulation. The agglutinations showed the heterogeneity of fibroblast populations. Conclusions: Stimulation with Con A showed that the fibroblast population had cell surface heterogeneity, and could respond in a different way to both CyA and cytokine stimulus. Moreover, increased synthesis of GAG in overgrown gingiva compared with synthesis in normal fibroblasts before CyA treatment suggests a possible genetic origin of damage. As not all CyA‐treated patients develop gingival overgrowth, a genetic predisposition may explain the different responses of gingival fibroblast populations.