TGF-beta(2) activates proliferative scar fibroblasts

Background. Cytokines, such as the transforming growth factor beta (TGF-bet a) isoforms, have been linked to the formation of proliferative scars. This study examines the stimulating effects of exogenous TGF-beta(2) on culture d keloid, burn hypertrophic scar, and normal skin fibroblasts and whether s uch effects can be suppressed with TGF-beta(2) antibody. Methods. In vitro, the fibroblast-populated collagen lattice (FPCL) is used in the evaluation of fibroblast activation by measuring contraction of the lattice over time. Primary cultures of fibroblasts were grown from keloids , burn hypertrophic scars, and normal skin using standard cell culture tech niques. TGF-beta(2) (10 ng/ml) was added to each of the three types of cell cultures and placed on prefabricated FPCLs. Each was tested against their normal control counterparts. TGF-beta(2) antibody (100 ng/ml) was then plac ed on the TGF-beta(2)-treated FPCLs. All lattices were allowed to contract and areas were measured for 5 days. Results. Compared to controls, keloid fibroblasts were most affected by the addition of exogenous TGF-beta(2). Normal skin fibroblasts did not show a significant increase in contraction early on, yet a significant difference was seen as time progressed. The addition of TGF-beta(2) antibody inhibited the function of keloid and burn hypertrophic scar fibroblasts. It also rev ersed the increased contraction of the TFG-beta(2)-treated proliferative sc ar fibroblasts. Conclusion. By utilizing an in vitro model, we have demonstrated that TGF-b eta(2) antibody reverses the increased contraction of FPCLs by proliferativ e scar fibroblasts treated with TGF-beta(2). This points to a possible trea tment modality in patients afflicted with this disfiguring problem. (C) 199 9 Academic Press.