RT Journal Article
SR Electronic
T1 Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA
JF Science
JO Science
FD American Association for the Advancement of Science
SP 393
OP 396
DO 10.1126/science.2783498
VO 243
IS 4889
A1 Raines, EW
A1 Dower, SK
A1 Ross, R
YR 1989
UL http://science.sciencemag.org/content/243/4889/393.abstract
AB Both interleukin-1 (IL-1) and platelet-derived growth factor (PDGF) induce proliferation of cultured fibroblasts and smooth muscle cells. These polypeptide mediators are released by activated macrophages and other cell types in response to injury and are thought to have a role in tissue remodeling and a number of pathologic processes. Analysis of the kinetics of [3H]thymidine incorporation by cultured fibroblasts demonstrated that the response to IL-1 is delayed approximately 8 hours relative to their response to PDGF. IL-1 transiently stimulated expression of the PDGF A-chain gene, with maximum induction after approximately 2 hours. Subsequent synthesis and release of PDGF activity into the medium was detected as early as 4 hours after IL-1 stimulation, and downregulation of the binding site for the PDGF-AA isoform of PDGF followed PDGF-AA secretion. Antibodies to PDGF completely block the mitogenic response to IL-1. Therefore, the mitogenic activity of IL-1 for fibroblasts and smooth muscle cells appears to be indirect and mediated by induction of the PDGF A-chain gene.