Tumor necrosis factor acts synergistically with autocrine interferon-beta and increases interferon-beta mRNA levels in human fibroblasts.
Medium of untreated human FS-4 foreskin fibroblasts contained a factor which, upon the addition of exogenous tumor necrosis factor (TNF), inhibited encephalomyocarditis virus replication when neither medium alone nor TNF alone were effective. This antiviral activity was abolished by a monoclonal antibody to human interferon (IFN)-beta, suggesting that the active component in the medium from untreated FS-4 cells was IFN-beta, present at subeffective concentrations. In addition, we show that untreated FS-4 cells contain IFN-beta mRNA, demonstrable by the highly sensitive polymerase chain reaction after reverse transcription. Treatment of FS-4 cells with TNF produced an approximately 16-fold increase in the steady-state level of IFN-beta mRNA. Our results support the conclusion that autocrine IFN-beta is secreted by untreated normal fibroblasts and that TNF can enhance the production of autocrine IFN-beta by increasing the level of IFN-beta mRNA. Our study also demonstrates that subeffective concentrations of autocrine IFN-beta, which escape detection in conventional assays, are sufficient to produce a strong synergistic action with TNF.
Reis
L F
LF
Department of Microbiology, New York University Medical Center, New York 10016.
Ho Lee
T
T
Vilcek
J
J
D000911:Antibodies, Monoclonal; D002460:Cell Line; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D005784:Gene Amplification; D005796:Genes / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha