Suppression of TNF-stimulated proliferation of diploid fibroblasts and TNF-induced cytotoxicity against transformed fibroblasts by TGF-beta.

Human transforming growth factor-beta (TGF-beta) dose-dependently inhibited proliferation of WI-38 cells, normal human diploid fibroblasts, stimulated by tumor necrosis factor (TNF). Inhibition occurred at 1 ng/ml concentration of TGF-beta. Also, TGF-beta dose-dependently suppressed cytotoxicity of TNF against L-929 cells, murine transformed fibroblasts. The concentration of TNF required for 50% cytolysis of L-929 cells was changed from 30 ng/ml to 350 ng/ml by 10 ng/ml TGF-beta. This suppression was abolished when L-929 cells were treated with actinomycin D or cycloheximide, suggesting that TGF-beta might inhibit the action of TNF via de novo protein synthesis. This response was not due to down regulation of TNF receptors nor to alteration of the affinity of TNF for its receptor.