GINGIVAL FIBROBLAST RESPONSE TO CYCLOSPORINE-A AND TRANSFORMING-GROWTH-FACTOR BETA(1)

This study investigates a potential role for TGF beta(1), in the patho genesis of cyclosporin A-induced gingival overgrowth (CsA-OG). TGF bet a(1) was localized immunohistochemically in the connective tissue of b oth normal gingiva and CsA-OG. Intense staining for TGF beta(1) was de tected at the tips of the dermal papillae of the overgrown gingiva. In addition, fibroblasts derived from healthy gingiva and fibroblasts de rived from CsA-OG were cultured both as monolayers or embedded in a 3D -collagen gel. Fibroblast activity was monitored in terms of protein a nd 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 mo nolayer culture TGF beta(1) significantly increased protein and collag en production in all cell strains (p < 0.05); however, there was no di fference in response between fibroblasts from overgrown and healthy ti ssue. The production of both protein and collagen was significantly lo wer in the presence of the combination of CsA and TGF beta(1) when com pared with the maximal stimulation produced by TGF beta(1) alone. In g el, TGF beta(1) significantly elevated matrix production by all overgr own 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 r educed protein and collagen production by overgrown cell strains compa red with TGF beta(1) alone. It is concluded that the cellular activity of gingival fibroblasts is dependant on culture conditions and that f ibroblasts derived from overgrown gingival tissue are more responsive to TGF beta(1) than normal gingival fibroblasts when cultured in type I collagen gel.