| First Author | Eigenbrod T | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 12 | Pages | 6533-41 |
| PubMed ID | 23667107 | Mgi Jnum | J:204860 |
| Mgi Id | MGI:5543565 | Doi | 10.4049/jimmunol.1300324 |
| Citation | Eigenbrod T, et al. (2013) Early inhibition of IL-1beta expression by IFN-gamma is mediated by impaired binding of NF-kappaB to the IL-1beta promoter but is independent of nitric oxide. J Immunol 190(12):6533-41 |
| abstractText | The significance of bacterial RNA recognition for initiating innate immune responses against invading pathogens has only recently started to be elucidated. Bacterial RNA is an important trigger of inflammasome activation, resulting in caspase-1-dependent cleavage of pro-IL-1beta into the active form. It was reported previously that prolonged treatment with IFN-gamma can inhibit IL-1beta production at the level of both transcription and Nlrp3 inflammasome activation in an NO-dependent manner. As a result of the delayed kinetics of NO generation after IFN-gamma stimulation, these effects were only observed at later time points. We report that IFN-gamma suppressed bacterial RNA and LPS induced IL-1beta transcription in primary murine macrophages and dendritic cells by an additional, very rapid mechanism that was independent of NO. Costimulation with IFN-gamma selectively attenuated binding of NF-kappaB p65 to the IL-1beta promoter, thus representing a novel mechanism of IL-1beta inhibition by IFN-gamma. Transcriptional silencing was specific for IL-1beta because expression of other proinflammatory cytokines, such as TNF, IL-6, and IL-12p40, was not affected. Furthermore, by suppressing IL-1beta production, IFN-gamma impaired differentiation of Th17 cells and production of neutrophil chemotactic factor CXCL1 in vitro. The findings provide evidence for a rapid immune-modulating effect of IFN-gamma independent of NO. |
