title: Effect on platelet-derived growth factor-induced mitogenesis of double-stranded RNA: evidence for an autocrine growth inhibition mediated by interferon-beta.
abstract: Stimulation of normal human foreskin fibroblasts with platelet-derived growth factor (PDGF) was inhibited by the addition of the synthetic double-stranded RNA polyinosinic-polycytidylic acid (poly-I:C) as measured by incorporation of 3H-thymidine (3H-TdR). Single-stranded polycytidylic or polyinosinic acid had no effect. Double-stranded RNA is an inducer of interferon-beta (IFN-beta) in fibroblasts. On the mRNA level, an expression of IFN-beta 2 but not of IFN-beta 1 was seen after addition of PDGF and/or poly-I:C. The inhibition of PDGF-induced mitogenesis was completely blocked by an antiserum to IFN-beta. Poly-I:C did not interfere with PDGF binding to its receptor, nor did it block protein synthesis, indicating that the inhibition is not due to a nonspecific toxic effect of the double-stranded RNA but rather is mediated by IFN-beta. The present study implies that the IFN-beta system in fibroblasts is a very potent autocrine inhibitory pathway.
authors.affiliation: Department of Pathology, University of Uppsala, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Forsberg
authors.forename: Y
authors.initials: Y
authors.lastname: Paulsson
authors.forename: B
authors.initials: B
authors.lastname: Westermark
mesh_terms: D002460:Cell Line; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D013997:Time Factors
chemical_list: D007370:Interferon Type I; D010982:Platelet-Derived Growth Factor; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D005346:Fibroblast Growth Factors; D017479:Receptors, Platelet-Derived Growth Factor; D011070:Poly I-C