Mitogenic effect of double-stranded RNA in human fibroblasts: role of autogenous interferon.
The synthetic double-stranded RNA polyinosinate-polycytidylate [poly(I).poly(C)] was mitogenic in cultures of human foreskin fibroblasts, as demonstrated by a stimulation of 3H-thymidine incorporation and an increase in cell density. Poly(I).poly(C) is a potent inducer of interferon (IFN)-beta in human fibroblasts. Single-stranded poly(l) or poly(C) were not mitogenic in human fibroblasts and did not stimulate IFN production. Antiserum to interferon (IFN)-beta, added to poly(I).poly(C)-stimulated cultures in order to neutralize endogenously generated IFN, markedly amplified the mitogenic action. Under similar experimental conditions, antiserum to IFN-beta did not enhance the mitogenic action of epidermal growth factor (EGF). Dexamethasone enhanced the mitogenic action of poly(I).poly(C) in a manner similar to antiserum against IFN-beta. This effect of dexamethasone correlated with its marked inhibitory action on poly(I).poly(C)-stimulated IFN production. Together with the results of other related studies, these findings support the notion of an evolutionary link between the generation of a mitogenic signal and IFN induction. In addition, these results support the concept that autocrine secretion of IFN-beta can exert negative feedback control of cell proliferation.
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007106:Immune Sera; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008934:Mitogens; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded; D012867:Skin / Q000166:cytology / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D007106:Immune Sera; D007370:Interferon Type I; D008934:Mitogens; D012330:RNA, Double-Stranded; D003907:Dexamethasone; D011070:Poly I-C; D013936:Thymidine