DEXAMETHASONE POTENTIATES THE STIMULATORY EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I ON COLLAGEN PRODUCTION IN CULTURED HUMAN FIBROBLASTS

We examined the effects of insulin-like growth factor-I (IGF-I) and dexamethasone on the production of collagen by cultures of human infant foreskin fibroblasts, and the interaction between these two factors. IGF-I at 500 ng/ml maximally increased collagen accumulation fourfold. Collagen was increased twofold relative to total protein production. Dexamethasone at a concentration of 1 mu mol/l reduced collagen production by between 25% and 40% in unstimulated cells and those cultured with up to 100 ng IGF-I/ml. However, dexamethasone did potentiate collagen production in cells stimulated with 250 ng IGF-I/ml. This potentiation was independent of any effects of IGF-I or dexamethasone on prostaglandin (PG)E(2) production. Transforming growth factor-beta (TGF-beta) is also a potent stimulator of collagen formation. However, no potentiation of TGF-beta-stimulated collagen production by dexamethasone was apparent. The mechanism by which dexamethasone potentiates IGF-I-stimulated collagen production was investigated. Dexamethasone treatment increased IGF-I binding to the type 1 IGF receptor without altering the binding affinity. Dexamethasone also attenuated the secretion of IGF-binding proteins by IGF-I-maintained cells.