Tumor Necrosis Factor α Induces Invasiveness of Human Skin Fibroblasts In Vitro

The chemotactic response of fibroblasts plays an important role during wound healing and fibrosis. Several substances have been found to mediate fibroblast migration in vitro. In the tissue, however, fibroblasts have also the potential to pass through connective tissue harriers following a chemotactic stimulus. Since tumor necrosis factor a (TNF α) is a cytokine released by mononuclear cells during wound healing, we have been interested in studying its effect on the regulation of fibroblast chemotaxis and invasive migration. TNF α did not attract skin fibroblasts nor did it alter their chemotactic response towards other chemoattractants like fibroblast conditioned medium or fibronectin. However, whereas normal skin fibroblasts did not invade a collagen I gel, preincubation of the cells with TNF a markedly induced their invasive migration into the gel. This seems to be associated with a specific degradation of type I collagen, because TNF α did not promote the invasion of skin fibroblasts through a reconstituted basement membrane (Matrigel)