Phorbol esters potentiate the induction of class I HLA expression by interferon alpha.
We have studied the effect of phorbol esters on the induction of class I histocompatibility antigen (HLA) expression by interferons (IFNs) in the T-cell line MOLT-4 and in the MOLT-4 mutant YHHH. Addition of IFN-alpha to phorbol 12,13-dibutyrate-pretreated MOLT-4 cells causes a greater than 20-fold increase in the expression of class I HLA, as compared to a 4- to 7-fold IFN-alpha-induced increase in control cells. Pretreatment with phorbol 12,13-dibutyrate does not alter the class I HLA response to IFN-gamma or the responses of other IFN-induced genes. This effect of phorbol 12,13-dibutyrate reproduces in MOLT-4 cells the phenotype of the mutant YHHH, which also displays a selective enhanced class I HLA response to IFN-alpha. Pretreatment of YHHH with phorbol 12,13-dibutyrate does not affect any of the responses induced by IFN. These findings suggest the existence of a phorbol ester-sensitive factor, inducible in MOLT-4 and constitutively expressed or modified in YHHH, which operates in the pathway of induction of class I HLA by IFN-alpha but not in the pathway used by IFN-gamma.
Erusalimsky
J D
JD
Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
Kefford
R F
RF
Gilmore
D J
DJ
Milstein
C
C
D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007945:Leukemia, Lymphoid; D009154:Mutation; D009693:Nucleic Acid Hybridization; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D007371:Interferon-gamma; D011493:Protein Kinase C