Gingival fibroblast response to cyclosporin A and transforming growth factor β1

This study investigates a potential role for TGFβ₁ in the pathogenesis of cyclosporin A-induced gingival overgrowth (CsA-OG). TGFβ₁ was localized immunohistochemically in the connective tissue of both normal gingiva and CsA-OG. Intense staining for TGFβ₁ 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 TGFβ₁ (ii) 500 ng/ml CsA, or (iii) 500 ng/ml CsA and 1 ng/ml TGFβ₁. In monolayer culture TGFβ₁ 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 TGFβ₁ when compared with the maximal stimulation produced by TGFβ₁ alone. In gel, TGFβ₁ 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 TGFβ₁ in gel cultures reduced protein and collagen production by overgrown cell strains compared with TGFβ¹ alone. It is concluded that the cellular activity of gingival fibroblasts is dependant on culture conditions and that fibroblasts derived from overgrown gingival tissue are more responsive to TGFβ₁ than normal gingival fibroblasts when cultured in type I collagen gel.