Aste-Amezaga, MiguelMa, XiaojingSartori, Alexandrina [UNESP]Trinchieri, Giorgio2014-05-272014-05-271998-06-15Journal of Immunology, v. 160, n. 12, p. 5936-5944, 1998.0022-1767http://hdl.handle.net/11449/65458Exogenously 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.5936-5944enginterleukin 10interleukin 12cellular immunitycontrolled studygene inductiongenetic transcriptionhumanhuman cellmonocytemononuclear cellpriority journalstaphylococcus aureustranscription regulationAnimalsCHO CellsCricetinaeCycloheximideGene Expression RegulationHumansInterleukin-10Interleukin-12KineticsLipopolysaccharidesMonocytesProtein Synthesis InhibitorsRNA, MessengerStaphylococcus aureusTime FactorsTranscription, GeneticTumor Necrosis Factor-alphaArtigoAcesso restrito2-s2.0-00325263384977572416129527