TGF-beta2 activates proliferative scar fibroblasts.
BACKGROUND
Cytokines, such as the transforming growth factor beta (TGF-beta) isoforms, have been linked to the formation of proliferative scars. This study examines the stimulating effects of exogenous TGF-beta2 on cultured keloid, burn hypertrophic scar, and normal skin fibroblasts and whether such effects can be suppressed with TGF-beta2 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 techniques. TGF-beta2 (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-beta2 antibody (100 ng/ml) was then placed on the TGF-beta2-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-beta2. 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-beta2 antibody inhibited the function of keloid and burn hypertrophic scar fibroblasts. It also reversed the increased contraction of the TFG-beta2-treated proliferative scar fibroblasts.


CONCLUSIONS
By utilizing an in vitro model, we have demonstrated that TGF-beta2 antibody reverses the increased contraction of FPCLs by proliferative scar fibroblasts treated with TGF-beta2. This points to a possible treatment modality in patients afflicted with this disfiguring problem.
Smith
P
P
Bay Pines Veterans Medical Center, Institute of Tissue Regeneration, Repair, and Rehabilitation, Bay Pines, Florida, 33744, USA.
Mosiello
G
G
Deluca
L
L
Ko
F
F
Maggi
S
S
Robson
M C
MC
D000906:Antibodies / Q000494:pharmacology; D002056:Burns / Q000150:complications; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002921:Cicatrix / Q000209:etiology / Q000473:pathology*; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D007627:Keloid / Q000473:pathology; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D016212:Transforming Growth Factor beta