Gingival fibroblast response to cyclosporin A and transforming growth factor β1

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Abstract
This study investigates a potential role for TGF beta 1 in the pathogenesis of cyclosporin A-induced gingival overgrowth (CsA-OG). TGF beta 1 was localized immunohistochemically in the connective tissue of both normal gingiva and CsA-OG. Intense staining for TGF beta 1 was detected at the tips of the dermal papillae of the overgrown gingiva. In addition, fibroblasts derived from healthy gingiva and fibroblasts derived from CsA-OG were cultured both as monolayers or embedded in a 3D-collagen gel. Fibroblast activity was monitored in terms of protein and collagen production in the presence of (i) 1 ng/ml TGF beta 1, (ii) 500 ng/ml CsA, or (iii) 500 ng/ml CsA and 1 ng/ml TGF beta 1. In monolayer culture TGF beta 1 significantly increased protein and collagen production in all cell strains (p < 0.05); however, there was no difference in response between fibroblasts from overgrown and healthy tissue. The production of both protein and collagen was significantly lower in the presence of the combination of CsA and TGF beta 1 when compared with the maximal stimulation produced by TGF beta 1 alone. In gel, TGF beta 1 significantly elevated matrix production by all overgrown cell strains (p < 0.05) but had little or no effect on the normal cell strains. The combination of CsA and TGF beta 1 in gel cultures reduced protein and collagen production by overgrown cell strains compared with TGF beta 1 alone. It is concluded that the cellular activity of gingival fibroblasts is dependent on culture conditions and that fibroblasts derived from overgrown gingival tissue are more responsive to TGF beta 1 than normal gingival fibroblasts when cultured in type I collagen gel.