Tumour necrosis factor a, interferon γ and dexamethasone regulate IGF-I-maintained collagen production in cultured human fibroblasts

Abstract

Abstract We examined the effects of tumour necrosis factor α (TNFα) and interferon γ (IFNγ) on the production of collagen by human infant foreskin fibroblasts. Collagen synthesis was maintained in the presence of IGF-I so that cytokine effects could be examined in the absence of serum. TNFα inhibited IGF-I-maintained collagen production in a dose-dependent manner. Maximal suppression of 50% was attained at a concentration of 7·5 ng/ml. IFNγ also suppressed collagen accumulation in IGF-I-maintained cells, with a maximal inhibition to 55% at 375 U/ml. The rate of collagen formation relative to total protein production for secreted proteins was calculated. This value decreased from 10·3% for IGF-I-cultured cells to 6·2% and 8·4% with the inclusion of TNFα and IFNγ respectively, indicating that inhibition was selective for collagen. TNFα (5 ng/ml) and IFNγ (250 U/ml) together suppressed IGF-I-maintained collagen production to approximately 35%, with a decrease from 10·3% to 2·9% in collagen production relative to total protein. The inclusion of a serum-free period prior to the addition of TNFα to the cultures resulted in a further inhibition to 15% of control. This increase in inhibition was not seen if dexamethasone was present in the serum-free period prior to cytokine addition. These data showed that IGF-Imaintained collagen formation is suppressed by the proinflammatory cytokines TNFα and IFNγ, and that these interactions are influenced by dexamethasone. Proinflammatory cytokines interact in a complex manner with other serum factors to modulate IGF-I-stimulated extracellular matrix production and may have important roles in regulating tissue repair. Journal of Endocrinology (1995) 147, 167–176