Phorbol ester-mediated inhibition of IFN-alpha/beta gene transcription in blood mononuclear leukocytes.
The phorbol ester PMA efficiently inhibits the in vitro IFN-alpha and -beta responses in human blood monocytes induced by Sendai virus and in natural IFN-producing cells induced by glutaraldehyde-fixed herpes simplex virus-infected human amnion (WISH) cells. This PMA-mediated inhibition of IFN-alpha/beta secretion is correlated with considerably reduced levels of IFN-alpha/beta mRNA, as determined by Northern blot analysis. Nuclear run-on assays further show that, at least in monocytes, PMA inhibits transcription of the IFN-alpha and -beta genes. The synthetic diacylglycerol 1-oleoyl-2-acetylglycerol has the same effects as PMA, and the protein kinase inhibitor staurosporine prevents the PMA-mediated inhibition of IFN-alpha/beta expression. These results suggest a role for protein kinase C in the inhibition of IFN-alpha/beta responses. The PMA does not inhibit the accumulation of IFN-beta mRNA in monocytes stimulated by Sendai virus in the presence of cycloheximide, indicating that the inhibitory action of the phorbol ester requires de novo protein synthesis.
Sandberg
K
K
Department of Veterinary Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Eloranta
M L
ML
Gobl
A E
AE
Alm
G V
GV
D000470:Alkaloids / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006561:Herpes Simplex / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D018184:Paramyxoviridae Infections / Q000276:immunology; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D018139:Simplexvirus / Q000276:immunology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D000470:Alkaloids; D004075:Diglycerides; D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta; C038237:1-oleoyl-2-acetylglycerol; D003513:Cycloheximide; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate