Tumor necrosis factor-induced expression of platelet-derived growth factor A-chain messenger RNA in fibroblasts.

Recombinant tumor necrosis factor (rTNF) induced a transient increase in the expression of the PDGF A-chain mRNA in FS-4 fibroblasts, as determined by Northern blot hybridization. The mRNA transcripts were of the expected sizes 1.9, 2.3, and 2.8 kb. Increased levels of the PDGF A-chain mRNA were detected 1, 2, and 4 h after addition of rTNF, the highest level being detected after 2 h. After 8 h the mRNA level was similar to that in control cultures. No PDGF B-chain mRNA (c-sis) could be detected following addition of rTNF. There was also an accumulation of PDGF receptor-competing activity in the medium of rTNF-exposed fibroblasts, suggesting that rTNF also induced the synthesis and release of functional PDGF A-chain homodimers (PDGF-AA). The fibroblast growth stimulatory activity in supernatants from rTNF-exposed fibroblasts could be neutralized by antiserum against rTNF, and thus rTNF seemed to be able to act as a direct mitogen. Hence rTNF-induced PDGF-AA is not the main mediator of rTNF's mitogenicity under the conditions investigated.