Production and secretion of platelet-derived growth factor AB by cultured human keratinocytes: regulatory effects of phorbol 12-myristate 13-acetate, etretinate, 1,25-dihydroxyvitamin D3, and several cytokines.
Platelet-derived growth factor (PDGF) is a potent mitogen for several mesenchymal cells and plays an important role in wound repair. Three PDGF isoforms, PDGF-AA, PDGF-BB, and PDGF-AB, have been found to be generated in various tissues. PDGF-AB production by normal human keratinocytes (NHKs), by human squamous cell carcinoma cell line (HSC-1) cells, and by human dermal fibroblasts (HDFs) was studied in the presence of agents which influence cell growth. Both NHKs and HSC-1 cells spontaneously produced and secreted PDGF-AB. NHKs grown in keratinocyte growth medium produced more PDGF-AB than did those grown in keratinocyte basic medium. Phorbol 12-myristate 13-acetate inhibited PDGF-AB production in NHKs but promoted its production in HSC-1 cells. 1,25-dihydroxyvitamin D3 up-regulated PDGF-AB production, whereas etretinate did not. High levels of calcium in the culture medium induced little change in cellular PDGF-AB levels. Prostaglandin E1 slightly inhibited PDGF-AB production, transforming growth factor beta 1 promoted PDGF-AB production and interferon-gamma, interleukin-1 alpha, and tumor necrosis factor-alpha failed to exert any influence at all. Cultured HDFs did not produce any detectable PDGF-AB. These results suggest that keratinocytes are a major source of cutaneous PDGF and that this factor may therefore play an important role in wound repair and in certain proliferative skin diseases.
Zhang
J Z
JZ
Department of Dermatology, Fukushima Medical College, Japan.
Maruyama
K
K
Ono
I
I
Kaneko
F
F
D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000494:pharmacology; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005050:Etretinate / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D003470:Culture Media; D016207:Cytokines; D004100:Dihydroxycholecalciferols; D010982:Platelet-Derived Growth Factor; D005050:Etretinate; C031699:23,25-dihydroxyvitamin D3; D013755:Tetradecanoylphorbol Acetate