Regulation of IL-2 receptor subunit genes in human monocytes. Differential effects of IL-2 and IFN-gamma.
We investigated the effects of IFN-gamma and IL-2 on IL-2R alpha and beta mRNA expression in human monocytes. Low basal expression of IL-2R beta mRNA was detected in fresh monocytes. Stimulation of monocytes with IL-2 induced a significant increase of IL-2R beta mRNA, but did not induce IL-2R alpha mRNA. In contrast, stimulation of monocytes with IFN-gamma-induced IL-2R alpha mRNA, but did not modify IL-2R beta mRNA. Five U/ml of IFN-gamma induced IL-2R alpha mRNA and 2.2 nM of IL-2 induced IL-2R beta mRNA, both within 3 h. Nuclear run-on experiments demonstrated that the induction of IL-2R alpha mRNA by IFN-gamma is controlled, at least in part, at the transcriptional level. In contrast, the enhancement of IL-2R beta mRNA by IL-2 is controlled at a posttranscriptional level and is associated with an increase in the half-life of IL-2R beta mRNA. The results of studies on the cytotoxic activity and on the expression of c-fms mRNA of monocytes activated by the combination of IFN-gamma and IL-2 show that pretreatment with IFN-gamma renders monocytes more sensitive to activation by IL-2. These results demonstrate that the IL-2R alpha and IL-2R beta subunits are induced by different lymphokines through distinct mechanisms and that both receptor subunits can influence the response of monocytes to IL-2.
Espinoza-Delgado
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Immunobiology Section, National Cancer Institute, Frederick Cancer Research Development Center, MD 21702-1201.
Longo
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DL
Gusella
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GL
Varesio
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D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015152:Blotting, Northern; D019002:CD56 Antigen; D002478:Cells, Cultured; D004357:Drug Synergism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma