TGF beta-like regulation of matrix metalloproteinases by anti-transforming growth factor-beta, and anti-transforming growth factor-beta 1 antibodies in dermal fibroblasts: Implications for wound healing.

Transforming growth factor beta (TGF-beta) stimulates collagen and matrix metalloproteinase-2 expression and inhibits MMP-1 expression in dermal fibroblasts. Anti-TGF-beta antibodies have been proposed in the prevention of wound scars. The goal of this research was to investigate the regulation of matrix metalloproteinases-1 and -2 expression at the protein, mRNA, and transcriptional levels using an anti-TGF-beta antibody to TGF-beta 1, 2, 3, and 5 (all isoforms), and specifically by an anti-TGF-beta 1 antibody. Both antibodies, though at doses lower than the recommended neutralization dose, stimulated the expression of TGF-beta, and exhibited TGF-beta-like regulation of the matrix metalloproteinases. The antibodies inhibited matrix metalloproteinase-1 protein, mRNA, and promoter activity. The protein levels of matrix metalloproteinase-2 were up-regulated to a greater extent than the matrix metalloproteinase-2 mRNA level by both antibodies. These effects of anti-TGF-beta and anti-TGF-beta 1 antibodies on matrix metalloproteinase regulation were mimicked by exogenous TGF-beta 1 but not rabbit or chicken IgG. We infer that the anti-TGF-beta1 isoform that forms part of the composition of the anti-TGF-beta antibody to all isoforms may be responsible for the feedback stimulation of TGF-beta and the resultant alterations in the expression of the matrix metalloproteinases by the anti-TGF-beta antibodies.