Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1beta are differentially regulated in human blood mononuclear cells and mouse spleen cells.
Interleukin (IL)-18, formerly called interferon gamma (IFN-gamma)-inducing factor, is biologically and structurally related to IL-1beta. A comparison of gene expression, synthesis, and processing of IL-18 with that of IL-1beta was made in human peripheral blood mononuclear cells (PBMCs) and in human whole blood. Similar to IL-1beta, the precursor for IL-18 requires processing by caspase 1. In PBMCs, mature but not precursor IL-18 induces IFN-gamma; in whole human blood stimulated with endotoxin, inhibition of caspase 1 reduces IFN-gamma production by an IL-1beta-independent mechanism. Unlike the precursor for IL-1beta, precursor for IL-18 was expressed constitutively in PBMCs and in fresh whole blood from healthy human donors. Western blotting of endotoxin-stimulated PBMCs revealed processed IL-1beta in the supernatants via an caspase 1-dependent pathway. However, in the same supernatants, only unprocessed precursor IL-18 was found. Unexpectedly, precursor IL-18 was found in freshly obtained PBMCs and constitutive IL-18 gene expression was present in whole blood of healthy donors, whereas constitutive IL-1beta gene expression is absent. Similar to human PBMCs, mouse spleen cells also constitutively contained the preformed precursor for IL-18 and expressed steady-state IL-18 mRNA, but there was no IL-1beta protein and no spontaneous gene expression for IL-1beta in these same preparations. We conclude that although IL-18 and IL-1beta are likely members of the same family, constitutive gene expression, synthesis, and processing are different for the two cytokines.
Puren
A J
AJ
Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Fantuzzi
G
G
Dinarello
C A
CA
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000097:blood / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D020382:Interleukin-18 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology; D014158:Transcription, Genetic
D007375:Interleukin-1; D020382:Interleukin-18; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma