Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism.
Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time-dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL-8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.
Bosco
M C
MC
Laboratory of Experimental Immunology, BRMP, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
Gusella
G L
GL
Espinoza-Delgado
I
I
Longo
D L
DL
Varesio
L
L
D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D015854:Up-Regulation
D016209:Interleukin-8; D012333:RNA, Messenger; D007371:Interferon-gamma