Diverse responses of human fibroblasts to a highly purified fibroblast-activating factor from the U937 line of human monocytes.
The responses of human dermal fibroblasts to highly purified fibroblast-activating factor (FAF), derived from supernatants of U937 human monocytes stimulated with phorbol myristate acetate (PMA), were investigated with several in vitro assays of specific synthetic functions. The highly purified peptide was detected as a single 16,000-18,000 MW protein, by both silver staining and Western blot analysis, with an antiserum generated against a synthetic peptide representing the amino-terminal sequence of 17 amino acids. At concentrations that induced similar levels of fibroblast proliferation, transforming growth factor-beta (TGF-beta), interleukin-1 (IL-1), acidic fibroblast growth factor (aFGF) and FAF also stimulated fibroblasts to generate and release prostaglandin E2 (PGE2) and proteoglycans. TGF-beta had the least effect on proteoglycan production. In contrast, the production and secretion of collagen evoked by FAF was only minimal when compared to that observed with IL-1 and aFGF. FAF and aFGF promoted fibroblast-induced collagen gel contraction with similar potency. Thus, the profile of fibroblast effects is a specific property of each cytokine.
Turck
C W
CW
Howard Hughes Medical Institute, San Francisco, California 94143-0724.
Kennedy
P W
PW
Schiogolev
S I
SI
Goetzl
E J
EJ
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002460:Cell Line; D010450:Endopeptidases; D005347:Fibroblasts / Q000187:drug effects; D018093:Gelatinases; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism*; D012697:Serine Endopeptidases; D012867:Skin / Q000187:drug effects*; D000099167:Fibroblast Activation Protein Alpha
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D006133:Growth Substances; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha