Up-regulation of cytokine mRNA in human monocytes and myeloid cell lines by the differentiation/activation factor p48.
Polypeptide 48 is a 48,000 MW protein, originally isolated from conditioned media of some human leukaemic cell lines, that induces differentiation and cytolytic activity in HL-60 promyelocytic leukaemia cells and activates human peripheral blood monocytes to secrete interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha). In the present study we examined the effects of p48 on the accumulation of a series of monokine transcripts, including TNF-alpha, IL-1 alpha, IL-1 beta and IL-6, in human peripheral blood monocytes and the myeloid/monocyte cell lines HL-60 and U937. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis, p48 was found to induce accumulation of TNF-alpha, IL-1 alpha and IL-1 beta mRNA in peripheral blood monocytes, HL-60 and U937 cells. IL-6 mRNA was found to be increased in p48-stimulated peripheral blood monocytes but not HL-60 or U937. Thus, the secretion of IL-1 and TNF-alpha by p48-stimulated monocytic cells was associated with up-regulation of cytokine mRNA, suggesting that p48 leads to increased transcription or mRNA stability in these cells. As U937 and HL-60 are likely to represent premonocyte stages of haemopoietic differentiation, it is possible that the effect of p48 on IL-6 mRNA, in contrast to its effect on TNF and IL-1, requires cells to be at a later differentiation step.
Department of Medicine, University of Tennessee Medical Center, Graduate School of Medicine, Knoxville, USA.
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DP
Kestler
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S
Agarwal
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Hall
D015152:Blotting, Northern; D002454:Cell Differentiation / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008565:Membrane Proteins / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C097656:polypeptide 48