Tamoxifen downregulates TGF-beta production in keloid fibroblasts

Keloids occur only in humans and are characterized by fibroblast overproduction of collagen types I and III. Keloid fibroblasts have been shown to make elevated levels of transforming growth factor beta (TGF-beta), a growth factor known to promote extracellular matrix production and fibrosis. Thus, the pathophysiology underlying keloid formation may be driven by the biological activity of TGF-beta. Tamoxifen, a synthetic, nonsteroidal antiestrogen has been shown to inhibit keloid fibroblast proliferation and decrease collagen production. The purpose of this study was to determine if a mechanism by which tamoxifen decreases keloid collagen production is through a downregulation of TGF-beta. Through a luciferase TGF-beta bioassay we found that 4 microM of tamoxifen generated a 49% reduction in total TGF-beta activity and 8 microM generated an 85% reduction compared with controls. Thus we propose that one of the mechanisms by which tamoxifen decreases keloid fibroblast collagen synthesis is by decreasing TGF-beta production.