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.
Paulsson
Y
Y
Department of Pathology, University Hospital, Uppsala, Sweden.
Austgulen
R
R
Hofsli
E
E
Heldin
C H
CH
Westermark
B
B
Nissen-Meyer
J
J
D001667:Binding, Competitive; D002478:Cells, Cultured; D003470:Culture Media; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003470:Culture Media; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors; D017479:Receptors, Platelet-Derived Growth Factor