Apolipoprotein E deficiency potentiates macrophage resistance to staphylococcus aureus osteomyelitis via regulating cholesterol metabolism
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE227521 | GEO | 2023/07/09
REPOSITORIES: GEO
Similar Datasets
Project description:We aimed to elucidate the mechanism of IL-27/ IL-27 receptor signaling effects on S. aureus osteomyelitis via gene expression studies.
2021-03-16 | GSE168896 | GEO
Project description:Staphylococcus aureus is the principal causative agent of osteomyelitis, a serious bacterial infection of bone that is associated with progressive inflammatory damage. Bone-forming osteoblasts have increasingly been recognized to play an important role in the initiation and progression of detrimental inflammation at sites of infection, and have been demonstrated to release an array of inflammatory mediators and factors that promote osteoclastogenesis and leukocyte recruitment following bacterial challenge. In the present study, we describe elevated bone tissue levels of the potent neutrophil-attracting chemokines, CXCL1, CXCL2, CXCL3, CXCL5, CCL3, and CCL7, in a murine model of post-traumatic staphylococcal osteomyelitis. RNA-Seq gene ontology analysis of isolated primary murine osteoblasts showed enrichment in differentially expressed genes involved in cell migration and chemokine receptor binding and chemokine activity following S. aureus infection, and a rapid increase in the expression of mRNA encoding CXCL1, CXCL2, CXCL3, CXCL5, CCL3, and CCL7, in these cells. Importantly, we have confirmed that such upregulated gene expression results in protein production with the demonstration that S. aureus challenge elicits the rapid and robust release of these chemokines by osteoblasts and does so in a bacterial dose-dependent manner. Furthermore, we have confirmed the ability of soluble osteoblast-derived chemoattractants to elicit the migration of a neutrophil-like cell line. As such, these studies demonstrate the robust production of CXCL1, CXCL2, CXCL3, CXCL5, CCL3, and CCL7, by osteoblasts in response to S. aureus infection, and the release of such neutrophil-attracting chemokines provides an additional mechanism by which osteoblasts could drive the inflammatory bone loss associated with staphylococcal osteomyelitis.
2022-11-12 | GSE217455 | GEO
Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.
2022-09-29 | GSE203564 | GEO
Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.
2022-09-29 | GSE203563 | GEO
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:The hypothesis that the squalene of olive oil might influence hepatic gene expression in an apoE and sex-dependent ways was tested in mice. Gene expression was analyzed using DNA microarrays in male apoE-deficient mice that received 1 g/kg/day of squalene for 10 weeks. As initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2 ratio > 1.5 or < -1.5) were further considered
2016-03-30 | E-GEOD-36932 | biostudies-arrayexpress
Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.
2022-10-03 | PXD034014 | Pride
Project description:The hypothesis that the squalene of olive oil might influence hepatic gene expression in an apoE and sex-dependent ways was tested in mice. Gene expression was analyzed using DNA microarrays in male apoE-deficient mice that received 1 g/kg/day of squalene for 10 weeks.
2016-03-30 | GSE36932 | GEO
Project description:The hypothesis that the oleanolic acid of olive oil might influence hepatic gene expression in an apoE was tested in mice. Gene expression was analyzed using DNA microarrays in male apoE-deficient mice that received 10 mg/kg/day of oleanolic acid for 11 weeks. As initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2 ratio > 1.5 or < -1.5) were further considered
2014-03-20 | E-GEOD-43589 | biostudies-arrayexpress
Project description:The anti-diabetic drug and agonist of the peroxisome proliferator-activated receptor gamma (Pparg), rosiglitazone, was recently withdrawn in many countries because the drug use was associated with an increased risk of heart failure. To investigate underlying pathomechanisms, we chose 6-month-old apolipoprotein E (apoE)-deficient mice, which are prone to atherosclerosis and insulin resistance, and thereby mimic the risk profile of patients with cardiovascular disease. After 8 weeks of rosiglitazone treatment (30 mg/kg/day), echocardiography and histology analyses demonstrated that rosiglitazone had induced heart failure with cardiac dilation. Concomitantly, cardiac lipid overload and lipid-induced cardiomyocyte death developed. The microarray gene expression study of heart tissue from rosiglitazone-treated apoE-deficient mice relative to untreated apoE-deficient mice and non-transgenic B6 mice identified cardiac Pparg-dependent lipid metabolism genes in rosiglitazone-treated mice, which seem to trigger a major heart failure promoting pathway. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) rosiglitazone-treated 8-month-old apolipoprotein (apoE)-deficient mice with symptoms of heart failure, (ii) untreated 8-month-old apoE-deficient mice, and (iii) age-matched, untreated, non-transgenic B6 control mice.
2011-03-18 | E-GEOD-28031 | biostudies-arrayexpress