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Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10.

TitleMolecular mechanisms of the induction of IL-12 and its inhibition by IL-10.
Publication TypeJournal Article
Year of Publication1998
AuthorsAste-Amezaga M, Ma X, Sartori A, Trinchieri G
JournalJ Immunol
Date Published1998 Jun 15
KeywordsAnimals, CHO Cells, Cricetinae, Cycloheximide, Gene Expression Regulation, Humans, Interleukin-10, Interleukin-12, Kinetics, Lipopolysaccharides, Monocytes, Protein Synthesis Inhibitors, RNA, Messenger, Staphylococcus aureus, Time Factors, Transcription, Genetic, Tumor Necrosis Factor-alpha

Exogenously added IL-10 rapidly inhibited Staphylococcus aureus- or LPS-induced cytokine mRNA expression in human PBMCs and monocytes, with a maximal effect observed when IL-10 was added from 20 h before until 1 h after the addition of the inducers. Nuclear run-on assays revealed that the inhibition of IL-12 p40, IL-12 p35, and TNF-alpha was at the gene transcriptional level and that the addition of IL-10 to S. aureus- or LPS-treated PBMCs did not affect mRNA stability. The inhibitory activity of IL-10 was abrogated by cycloheximide (CHX), suggesting the involvement of a newly synthesized protein(s). The addition of CHX at 2 h before S. aureus or LPS also inhibited the accumulation of IL-12 p40 mRNA, but did not inhibit IL-12 p35 and TNF-alpha mRNA. This finding suggests that p40 transcription is regulated through a de novo synthesized protein factor(s), whereas the addition of CHX at 2 h after S. aureus activation caused superinduction of the IL-12 p40, IL-12 p35, and TNF-alpha genes. These results indicate that in human monocytes, the mechanism(s) of IL-10 suppression of both IL-12 p40 and IL-12 p35 genes is primarily seen at the transcriptional level, and that the induction of the IL-12 p40 and p35 genes have different requirements for de novo protein synthesis.

Alternate JournalJ Immunol
PubMed ID9637507
Grant ListCA10815 / CA / NCI NIH HHS / United States
CA20833 / CA / NCI NIH HHS / United States
CA32898 / CA / NCI NIH HHS / United States

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