Biphasic effects of pleiotropic cytokine IL-27 during Staphylococcus aureus implant-associated osteomyelitis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE168896 | GEO | 2021/03/16
REPOSITORIES: GEO
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Project description:Biphasic effects of pleiotropic cytokine IL-27 during Staphylococcus aureus implant-associated osteomyelitis
| PRJNA714525 | ENA
Project description:Objective: To investigate the molecular pathogenesis of bone with implant-associated osteomyelitis (IAOM) in early and chonic stages. Methods: After a 2 mm sterile stainless pin (0.3 mm in diameter) was inserted into the bone marrow cavity, 2 μl S. aureus solution at 1 × 10e6 CFU/ml was slowly injected into the bone marrow cavity using a micro-syringe to create IAOM mice while only an equal volume of sterile PBS to create controls. Transcriptomic sequencing was performed on day 3 and 14 post-operation, respectively. Differential expression analyses of IAOM_3D vs Ctrl_3D and of IAOM _14D vs Ctrl_14D were performed using the DESeq2 R package (1.16.1); P-values were adjusted using the Benjamini and Hochberg’s approach to control the false discovery rate. The genes with an adjusted P-value < 0.05 and |log2 (Fold Change)| > 1 were recognized as differentially expressed genes (DEGs). GO, KEGG and PPI analysis of DEGs were performed to identify key genes. Results: Differential expression analyses detected a total of 101 DEGs, among which 96 were up-regulated and 5 down-regulated in the femur, when the IAOM and control groups were compared by day 3 post-infection. The number of DEGs significantly increased up to 1,702 by day 14 post-operation, with 1,065 up-regulated and 637 down-regulated in the IAOM femurs compared with controls. Further GO, KEGG and PPI analyses of DEGs suggested that IL-6, CXCL10, IFN-γ and CXCL9 were associated with early development of IAOM. Conclusions: Our study has revealed transcriptomic characteristics of IAOM and suggested that IL-6, CXCL10, IFN-γ and CXCL9 might play an important role in the early stage of IAOM.
2021-02-11 | GSE166522 | GEO
Project description:To explore how APOE functions in the mechanism of regulation of cholesterol metabolism during S. aureus osteomyelitis, we established S. aureus osteomyelitis models in WT mice and APOE knockout mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of bone marrow from mice mentioned above at day 7 after operation.
2023-07-09 | GSE227521 | GEO
Project description:IL-6 and IL-27 have antagonistic and overlapping functions, signal through a shared receptor subunit and employ the same downstream STAT proteins. To evaluate the degree of specificity and redundancy for these cytokines, we quantified global transcriptomic changes induced by the two cytokines and determined the relative contributions of STAT1 and STAT3 using genetic models and ChIP-seq. We found a high degree of overlap of the transcriptomes induced by IL-6 and IL-27 and extremely few examples in which the cytokines acted in opposition. Using STAT deficient cells and T cells from patients with gain-of-function STAT1 mutations, we show that STAT3 was responsible for the overall transcriptional output driven by both cytokines, whereas STAT1 was the driver of cytokine specificity. STAT1 did not compensate for the lack STAT3; on the contrary, much of STAT1 binding to chromatin was STAT3 dependent. Thus, STAT1 shapes the specific cytokine signature superimposed upon STAT3’s action. Integrated analysis of transcriptome and transcription factor binding data from cytokine treated CD4+T cells
2015-05-27 | E-GEOD-65621 | biostudies-arrayexpress
Project description:High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis infection
| PRJEB6003 | ENA
Project description:IL-6 and IL-27 have antagonistic and overlapping functions, signal through a shared receptor subunit and employ the same downstream STAT proteins. To evaluate the degree of specificity and redundancy for these cytokines, we quantified global transcriptomic changes induced by the two cytokines and determined the relative contributions of STAT1 and STAT3 using genetic models and ChIP-seq. We found a high degree of overlap of the transcriptomes induced by IL-6 and IL-27 and extremely few examples in which the cytokines acted in opposition. Using STAT deficient cells and T cells from patients with gain-of-function STAT1 mutations, we show that STAT3 was responsible for the overall transcriptional output driven by both cytokines, whereas STAT1 was the driver of cytokine specificity. STAT1 did not compensate for the lack STAT3; on the contrary, much of STAT1 binding to chromatin was STAT3 dependent. Thus, STAT1 shapes the specific cytokine signature superimposed upon STAT3’s action.
2015-05-27 | GSE65621 | GEO
Project description:The pleiotropic cytokine IL-27 is essential for the clearance of the persistent LCMV strain Clone 13, however the cellular sources of IL-27 during viral infection are incompletely mapped and their relative importance unknown. Here we utilised single-cell RNA-sequencing of splenocytes from IL27-p28-GFP mice infected with Clone 13 to quantify the temporal patterns of IL-27 p28 production. IL-27-p28-GFP+ and IL-27-p28-GFP- splenocytes were sorted at 4 timepoints during Clone 13 infection and analysed by 3' single-cell transcriptome sequencing. Dendritic cells were major producers of early IL-27 with macrophages and monocytes being the predominant IL-27 producers during acute and persistent phases of infection. Interestingly, we also identified activated B cells and plasma cells as a prominent subset of IL-27-producing splenocytes and through B-cell-specific deletion of IL-27-p28 demonstrated that B-cell derived IL-27 is essential for sustained function of CD4 T cells and eventual clearance of Clone 13.
2022-01-10 | GSE186898 | GEO
Project description:Interleukin 27 (IL-27) is a member of the IL-6 and/or IL-12 family that elicits both pro- and anti-inflammatory responses. Interferons (IFNs) are a family of cytokines that activate the JAK-STAT signaling pathway to induce an antiviral state in cells. Recent studies have reported that IL-27 also induces a robust antiviral response against diverse viruses, both in vitro and in vivo, suggest that IFNs and IL-27 share many similarities at the functional level. However, it is still unknown how similar or different IFN- and IL-27-dependent signaling pathways are. We reported that IFNs and IL-27 activate JAK-STAT signaling and induce shared pro-inflammatory and antiviral pathways in monocyte-derived macrophages (MDMs), leading to the common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs). Importantly, the ability of IL-27 to induce those responses is independent of IFN induction and cellular lineage. Additionally, functional analysis demonstrated that like IFNs, IL-27-mediated response reduced chikungunya and dengue viruses replication in MDMs. In summary, IL-27 exhibits properties similar to those of all three types of human IFN, including the ability to stimulate a protective antiviral response.
2024-04-15 | GSE262963 | GEO
Project description:IL-27, a member of the IL-12- family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune-regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-, induces the expression of IL-18BP, IDO and PD-L1 immune-regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN- display a broad overlap of functions on human ovarian cancer cells. Indeed, among 990 proteins modulated by either cytokine treatment in SKOV3 cells, 814 showed a concordant modulation by both cytokines, while a smaller number (176) were differentially modulated. The most up-regulated proteins were common to both IFN-γ and IL-27. In addition, functional analysis of IL-27- regulated protein networks highlighted pathways of interferon signaling and regulation, antigen presentation, protection from natural killer cell-mediated cytotoxicity, regulation of protein polyubiquitination and proteasome, aminoacid catabolism and regulation of viral protein levels.
2017-05-19 | PXD004419 | Pride
Project description:Interleukin-27 (IL-27) can partially reduce tumor growth in several animal models, including pros-tate cancer. We describe our findings on the effects of IL-27 gene delivery on prostate cancer cells and how sequential therapy with IL-18 enhances the efficacy of IL-27. We applied IL-27 and IL-18 deliv-ery with the goal of reducing prostate tumor growth, first in cell culture and then in an immunocom-petent mouse model. The combination of IL-27 followed by IL-18 (2718) successfully reduced can-cer cell viability, with significant effects found for a particular combination sequence. Interestingly, when we compared the 2718 combination with a single cytokine targeted to IL-6R via an oligo-peptide (27pepL) recently developed by our group, we observed similar efficacy. This efficacy was further enhanced when 27pepL was sequenced with IL-18 (27pepL18)
2021-07-27 | GSE178142 | GEO