Effect on platelet‐derived growth factor‐induced mitogenesis of double‐stranded RNA: Evidence for an autocrine growth inhibition mediated by interferon‐β

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 3 H‐thymidine ( 3 H‐TdR). Single‐stranded polycytidylic or polyinosinic acid had no effect. Double‐stranded RNA is an inducer of interferon‐β (IFN‐β) in fibroblasts. On the mRNA level, an expression of IFN‐β 2 but not of IFN‐β 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‐β. 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‐β. The present study implies that the IFN‐β system in fibroblasts is a very potent autocrine inhibitory pathway.