Cytokine induction of interleukin-24 in human peripheral blood mononuclear cells.
Interleukin-24 (IL-24) is a recently identified member of the IL-10 family of cytokines. It was originally identified as a tumor suppressor molecule, melanoma differentiation-associated gene 7, and then renamed IL-24 and classified as a cytokine, based on its chromosomal location in the IL-10 locus, its mRNA expression in leukocytes, and its secretory sequence elements. Here, we correlate the kinetics of IL-24 mRNA and protein expression in human peripheral blood mononuclear cells (PBMC) stimulated by polyclonal activators phytohemagglutinin (PHA) and lipopolysaccharide (LPS) or by allogeneic major histocompatibility complex. PHA-stimulated PBMC express IL-24 mRNA, reaching peak levels at 8-12 h after stimulation. Protein expression, as measured by intracellular flow cytometry, followed the message, reaching maximum expression at 24 h. Subset analysis of mitogen-stimulated PBMC showed that IL-24 was expressed primarily in T cells and macrophages. Expression of IL-24 in mitogen-stimulated PBMC is the result of cytokine stimulation. Individual cytokines including IL-2, IL-7, IL-15, tumor necrosis factor alpha, granulocyte macrophage-colony stimulating factor, and IL-1beta stimulate the expression of IL-24 mRNA and protein, whereas interferons and T helper cell type 2 cytokines fail to induce substantial IL-24. When LPS- or PHA-stimulated cells were treated with Actinomycin D, IL-24 mRNA persisted at high levels over the 4-h course of treatment. These data strongly suggest that the expression of IL-24 in human PBMC results from cytokine stimulation and is regulated at the post-transcriptional level through stabilization of IL-24 mRNA.
Experimental Therapeutics, Box 362, 1515 Holcombe Blvd., Houston, TX 77030, USA. npoindex@mdanderson.org
Nancy J
NJ
Poindexter
Eugene T
ET
Walch
Sunil
S
Chada
Elizabeth A
EA
Grimm
D000906:Antibodies / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D000099180:Interleukin-24
D000906:Antibodies; D016207:Cytokines; D003609:Dactinomycin; D007378:Interleukins; D008070:Lipopolysaccharides; D008934:Mitogens; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D000099180:Interleukin-24