Molecular mechanisms of the induction of IL-12 and its inhibition by IL- 10
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Data
1998-06-15
Autores
Aste-Amezaga, Miguel
Ma, Xiaojing
Sartori, Alexandrina [UNESP]
Trinchieri, Giorgio
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Resumo
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-α 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-α 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-α 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.
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interleukin 10, interleukin 12, cellular immunity, controlled study, gene induction, genetic transcription, human, human cell, monocyte, mononuclear cell, priority journal, staphylococcus aureus, transcription regulation, Animals, 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
Como citar
Journal of Immunology, v. 160, n. 12, p. 5936-5944, 1998.