Regulation of human IL-18 mRNA expression.
As virtually nothing is known about the pattern of expression of human IL-18, we investigated certain factors that may contribute to the regulation of IL-18 mRNA accumulation and compared this with regulation of the human gene encoding the p40 chain of IL-12, a cytokine that shares similar biologic activity with IL-18. IL-18 mRNA was expressed constitutively in unstimulated PBMC or monocytes, unlike p40, which required induction by a stimulus. Upon stimulation, IL-18 transcript accumulation was enhanced with an earlier and more transient pattern of expression than IL-12 p40 mRNA. Bacteria-derived stimuli and priming with IFN-gamma or IL-4 also upregulated IL-18 mRNA in a fashion similar to that of IL-12 p40. IL-10 exerted an inhibitory effect on IL-18 mRNA accumulation, though not as markedly as in the suppression of IL-12 p40 by IL-10. Finally, unlike IL-12 p40 mRNA, the constitutive accumulation of IL-18 transcripts by unstimulated cells was amplified in the presence of the translational blocker cycloheximide, which also caused a superinduction of IL-18 expression after Staphylococcus aureus stimulation.
Marshall
J D
JD
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania, 19104, USA.
Aste-Amézaga
M
M
Chehimi
S S
SS
Murphy
M
M
Olsen
H
H
Trinchieri
G
G
D015152:Blotting, Northern; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D020382:Interleukin-18 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020382:Interleukin-18; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D003513:Cycloheximide