Tumor necrosis factor-α inhibits collagen synthesis in human and rat granulation tissue fibroblasts

Abstract
The purpose of the study was to examine the effects of tumor necrosis factor-α (TNF-α) on collagen gene expression in rat and human granulation tissue fibroblast cultures. The cells were exposed to 0.1, 1, 10, or 100 ng/ml of TNF-α, and the rate of collagen synthesis was measured as synthesis of protein-bound3H-hydroxyproline. Total cellular RNA was isolated from fibroblasts, and measurements of specific cellular RNAs from fibroblasts were performed by Northern blot hybridizations using32P-labeled cDNA probes. In cultures of rat granulation tissue fibroblasts TNF-α decreased3H-hydroxyproline production to about 75% of that in controls and it also decreased proα1(I) and proα1(III) collagen mRNA levels, maximally to 33% and 23% of the control levels, respectively. In cultures of human granulation tissue fibroblasts a similar inhibiting effect in the production of collagen was seen. TNF-α decreased the production of3H-hydroxyproline to 56% of the control value with a dose of 100 ng/ml also having an inhibiting effect on proα1(I) collagen mRNA levels of up to 43% of the control level. However, no effect was seen on proα1(III) collagen mRNA levels.

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