Selective modulation of IFN-gamma mRNA stability by IL-12/NKSF.
We investigated the role of IL-12 in regulating IL-2 and IFN-gamma production in primary culture of human T cells. Addition of neutralizing antiserum against the 40-kDa subunit of IL-12 to PHA-stimulated PBMC markedly reduced both IFN-gamma protein production and mRNA accumulation and stability. Moreover, concurrent treatment of partially purified T cells (> 90% CD3+) with PHA and rIL-12 selectively enhanced IFN-gamma mRNA stability and protein production, while IL-2 protein and mRNA levels were unaffected. These studies also show that IFN-gamma and IL-2 mRNA stability are temporally dissociated during the course of T cell activation, and we propose that this dissociation may be mediated through the production of IL-12. The effect of IL-12 on modulation of IFN-gamma mRNA turnover is not associated with detectable changes in either the levels or affinity of cytoplasmic RNA-binding proteins capable of recognizing AU-rich sequences in the 3'UTR of IFN-gamma mRNA.
Nagy
E
E
Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756.
Buhlmann
J E
JE
Henics
T
T
Waugh
M
M
Rigby
W F
WF
D001483:Base Sequence; D002352:Carrier Proteins; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007106:Immune Sera; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics*; D018664:Interleukin-12 / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes
D002352:Carrier Proteins; D007106:Immune Sera; D007376:Interleukin-2; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma