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 mumol/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)E2 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.
Bird
J L
JL
Department of Tissue Physiology, Strangeways Research Laboratory, Cambridge, UK.
Tyler
J A
JA
D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013268:Stimulation, Chemical; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D003094:Collagen; D017526:Receptor, IGF Type 1; D015232:Dinoprostone