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.
Chau
D
D
Department of Surgery, New York University Medical Center, NY 10016, USA.
Mancoll
J S
JS
Lee
S
S
Zhao
J
J
Phillips
L G
LG
Gittes
G K
GK
Longaker
M T
MT
D018929:Cell Culture Techniques; D015536:Down-Regulation; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007627:Keloid; D008156:Luciferases; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D004965:Estrogen Antagonists; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D008156:Luciferases