Modulation of interleukin-1 receptor expression and interleukin-1 response in fibroblasts by platelet-derived growth factor

Our studies have revealed that the interleukin-1 (IL-1) receptors and response in BALB/c/3T3 fibroblasts are modulated by platelet-derived growth factor (PDGF). Incubation of quiescent cultures of BALB/c/3T3 fibroblasts with PDGF resulted in 4-5 fold higher 125I-IL-1 binding than the untreated cultures. Scatchard analysis showed that the increased 125I-IL-1 binding by PDGF-treated cells was due to a net increase in cell surface IL-1 receptors with no apparent change in binding affinity. The PDGF-induced increase of 125I-IL-1 binding was blocked by inhibitors of transcription, suggesting that a transcriptional event, perhaps a de novo synthesis of IL-1 receptors, is required for PDGF response. In a culture medium depleted of serum factors, IL-1 alone produced only a marginal (40-50%) increase in DNA synthesis in BALB/c/3T3 cells. In cells first exposed to PDGF, IL-1 produced 8-10-fold higher DNA synthesis than the controls. These findings provide evidence that IL-1 action in fibroblast may be regulated at the level of receptor expression.