Induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation.
Earlier studies showed that tumor necrosis factor (TNF) exerts a mitogenic effect in human diploid fibroblasts. Here we demonstrate that purified E. coli-derived recombinant human TNF inhibits encephalomyocarditis virus replication in "aged" human fibroblasts. Addition of neutralizing antibodies to human beta interferon (IFN-beta) blocked the antiviral action of TNF, indicating that this action is mediated by the generation of IFN-beta. We also show that antiserum to IFN-beta enhanced the mitogenic effect of TNF in confluent, serum-starved human fibroblasts, suggesting that induction of IFN-beta by TNF represents a physiological negative feedback mechanism regulating cell proliferation. Blot hybridization analysis of cytoplasmic polyadenylated RNA showed that TNF induced IFN-beta 2 mRNA, whereas no induction of IFN-beta 1 mRNA could be demonstrated. The results suggest that IFN-beta 2 has biological functions distinct from the other interferons.
Kohase
M
M
Henriksen-DeStefano
D
D
May
L T
LT
Vilcek
J
J
Sehgal
P B
PB
D000906:Antibodies / Q000276:immunology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004686:Encephalomyocarditis virus / Q000502:physiology; D005246:Feedback; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D011061:Poly A / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha; D014779:Virus Replication / Q000187:drug effects*
D000906:Antibodies; D006023:Glycoproteins; D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011061:Poly A