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.
Bonin
P D
PD
Upjohn Company, Kalamazoo, Michigan 49001.
Singh
J P
JP
D000818:Animals; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D013997:Time Factors
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D003609:Dactinomycin