Staphylococcus aureus infection induces the production of the neutrophil chemoattractants CXCL1, CXCL2, CXCL3, CXCL5, CCL3, and CCL7 by osteoblasts
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA899024 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22215314.fastq.gz | Fastqsanger.gz | |||
| SRR22215315.fastq.gz | Fastqsanger.gz | |||
| SRR22215316.fastq.gz | Fastqsanger.gz | |||
| SRR22215317.fastq.gz | Fastqsanger.gz | |||
| SRR22215318.fastq.gz | Fastqsanger.gz |
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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 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 posttraumatic staphylococcal osteomyelitis. RNA sequencing (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 chemokines 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.
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Project description:Macrophage polarization and synovitis play significant roles in rheumatoid arthritis (RA). Chemokines are involved almost throughout the entire pathology of synovitis. However, the interaction between chemokines and macrophage polarization in RA has been seldom reported. This study found that chemokine C-C motif ligand 7 (CCL7) secreted by polarized M1 macrophages enhances M1 polarization, creating a positive feedback loop and revealing the role of CCL7 in the progression of rheumatoid arthritis. In this research, RNA sequencing indicated that M1 polarized macrophages secrete a large amount of CCL7, which further enhances M1 polarization. Through immunohistochemistry and enzyme-linked immunosorbent assay, it was found that the expression of CCL7 in the synovial tissue and serum of RA patients and mice was upregulated. Intra-articular injection of CCL7 recombinant protein exacerbated M1 polarization of macrophages, inflammation, fibrosis in the synovial tissue, and worsened arthritis pain in mice, which was improved after the injection of CCL7 neutralizing antibody. In addition, CCL7 promoted M1 polarization of macrophages and reversed the M2 polarization induced by IL-4, and it also promoted macrophage proliferation and migration. Although it had an inhibitory effect on chondrocyte activity, it did not show a significant impact on chondrocyte metabolism. Mechanistically, CCL7 targets CCR1 to promote M1 polarization of macrophages, a process partly mediated through the activation of the JAK2/STAT1 pathway. When stimulated by CCL7, macrophages secreted a vast amount of pro-inflammatory factors, exacerbating synovitis and cartilage damage, leading to the aggravation of RA disease. Our research established a positive feedback loop between M1 polarization of macrophages and CCL7, indicating that blocking CCL7 could improve the progression of RA, suggesting CCL7 as a potential target for RA treatment.
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