Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE83615 | GEO | 2016/09/09
SECONDARY ACCESSION(S): PRJNA326501
REPOSITORIES: GEO
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Project description:The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs. These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.
2016-09-09 | GSE83613 | GEO
Project description:The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs. These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.
2016-09-09 | GSE83612 | GEO
Project description:Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia
| PRJNA326501 | ENA
Project description:Nrf2 regulates the transcriptional response to oxidative stress. These studies tested the role of Nrf2 during Streptococcus pneumoniae pneumonia and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils. Nrf2 null and wild type (WT) mice were studied at 6 and 24 h after instillation of S. pneumoniae or PBS. At 6 h, fewer neutrophils were recruited and the number of bacteria remaining in the lungs tended to be less (p = 0.06) in the Nrf2 null compared with WT mice. In uninfected lungs, 53 genes were already differentially expressed in Nrf2 null compared with WT mouse lungs, and gene sets involved in phagocytosis, Fc receptor function, complement, and Ig regulation are enhanced in PBS-treated Nrf2 null gene profiles compared with those of WT mice. These results suggest that initial host defense is enhanced in Nrf2 null mice, resulting in less recruitment of neutrophils. At 24 h, neutrophil recruitment was greater. The percentages of early apoptotic and late apoptotic/necrotic neutrophils were similar. At increasing inoculum numbers, mortality rates strikingly increased from 15 to 31 and 100% in Nrf2 null mice, whereas all WT mice survived, and Nrf2 null mice had a defect in clearance, particularly at the intermediate dose. The mortality was due to enhanced lung injury and greater systemic response. Gene profiling identified differentially regulated genes and pathways in neutrophils and lung tissue, including those involved in redox stress response, metabolism, inflammation, immunoregulatory pathways, and tissue repair, providing insight into the mechanisms for the greater tissue damage and increased neutrophil accumulation.
| S-EPMC5026972 | biostudies-literature
Project description:The complex role of neutrophils in modulating the inflammatory response is increasingly appreciated. Our studies profiled the expression of mRNAs and microRNAs (miRs) in lung neutrophils in mice during S. pneumoniae pneumonia and performed in depth in silico analyses. Lung neutrophils were isolated 24 hours after intratracheal instillation of PBS or S. pneumoniae, and differentially expressed (DE) mRNAs and miRs were identified. Lung neutrophils from mice with S. pneumoniae pneumonia contained 4127 DE mRNAs, 36% of which were upregulated at least 2-fold. During pneumonia, lung neutrophils increase expression of pattern recognition receptors, receptors for inflammatory mediators, transcription factors including NF-κB and AP-1, Nrf2 targets, cytokines, chemokines and other inflammatory mediators. Interestingly, neutrophils responded to Type I interferons, whereas they both produced and responded to Type II interferon. Expression of regulators of the inflammatory and immune response was verified at the mRNA and protein level. Of approximately 1100 miRs queried, 31 increased and 67 decreased more than 2-fold in neutrophils from S. pneumoniae pneumonia. Network analyses of potential DE miR-target DE mRNA interactions revealed candidate key regulatory miRs. Thus, S. pneumoniae modulates mRNA and miR expression by lung neutrophils, increasing their ability to respond and facilitating host defense.
| S-EPMC5595893 | biostudies-literature
Project description:Bacterial pneumonia is a common public health problem associated with significant mortality, morbidity, and cost. Neutrophils are usually the earliest leukocytes to respond to bacteria in the lungs. Neutrophils rapidly sequester in the pulmonary microvasculature and migrate into the lung parenchyma and alveolar spaces, where they perform numerous effector functions for host defense. Previous studies showed that migrated neutrophils produce IFN-? early during pneumonia induced by Streptococcus pneumoniae and that early production of IFN-? regulates bacterial clearance. IFN-? production by neutrophils requires Rac2, Hck/Lyn/Fgr Src family tyrosine kinases, and NADPH oxidase. Our current studies examined the mechanisms that regulate IFN-? production by lung neutrophils during acute S. pneumoniae pneumonia in mice and its function. We demonstrate that IFN-? production by neutrophils is a tightly regulated process that does not require IL-12. The adaptor molecule MyD88 is critical for IFN-? production by neutrophils. The guanine nucleotide exchange factor CalDAG-GEFI modulates IFN-? production. The CD11/CD18 complex, CD44, Toll-like receptors 2 and 4, TRIF, and Nrf2 are not required for IFN-? production by neutrophils. The recently described neutrophil-dendritic cell hybrid cell, identified by its expression of Ly6G and CD11c, is present at low numbers in pneumonic lungs and is not a source of IFN-?. IFN-? produced by neutrophils early during acute S. pneumoniae pneumonia induces transcription of target genes in the lungs, which are critical for host defense. These studies underline the complexity of the neutrophil responses during pneumonia in the acute inflammatory response and in subsequent resolution or initiation of immune responses.
| S-EPMC4370257 | biostudies-literature
Project description:PurposeIt is well known that age is related to the incidence of Mycoplasma pneumoniae pneumonia (MPP), and how age and other factors contribute to MPP remains unclear. In this study, we investigate how age affects the prognosis of MPP.Patients and methodsA total number of 1875 hospitalized children with pneumonia were enrolled in this study, including 52 children with refractory M. pneumoniae pneumonia (RMPP) and 298 children with non-RMPP. We used multiple logistic regression analysis to further identify the risk factors of RMPP, and found that age and polymorphonuclear neutrophils (PMNs) count were the key independent risk factors for the occurrence of RMPP. In order to improve specificity, 4.5 years old was taken as the cut-off value. Then, according to the cut-off value of age, 76 participants were recruited and divided into four groups: <4.5y MPP group, ≥4.5y MPP group, <4.5y health control (<4.5yHC) and ≥4.5y HC group. We explored the diverse functions of primary PMNs from children of different ages with MPP at cellular level. Besides, we studied the relationship between lung injury and PMNs in mice model with MPP of different ages.ResultsWe found that the age and PMNs count of RMPP group were significantly higher than those of the non-RMPP group. Importantly, there is a linear correlation between the age of patients with RMPP and the percentage of PMNs. Further analysis showed that elderly patients infected with M. pneumoniae had more active PMNs function. Meanwhile, proteomics showed that children with M. pneumoniae infection in different age groups have differences in PMNs apoptosis, nicotinamide adenine dinucleotide phosphate, mitochondrial function and oxidative stress. Finally, we found that age is also involved in the pathogenesis of mouse model with MPP.ConclusionWe speculate that age may contribute to the development of RMPP.
| S-EPMC8374848 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-11-01 | GSE97922 | GEO
Project description:BackgroundOxidative stress is heavily implicated in the pathogenic process of Parkinson's disease. Varying capacity to detoxify radical oxygen species through induction of phase II antioxidant enzymes in substantia nigra may influence disease risk. Here, we hypothesize that variation in NFE2L2 and KEAP1, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson's disease.MethodsThe study included a Swedish discovery case-control material (165 cases and 190 controls) and a Polish replication case-control material (192 cases and 192 controls). Eight tag single nucleotide polymorphisms representing the variation in NFE2L2 and three representing the variation in KEAP1 were chosen using HapMap data and were genotyped using TaqMan Allelic Discrimination.ResultsWe identified a protective NFE2L2 haplotype in both of our European case-control materials. Each haplotype allele was associated with five years later age at onset of the disease (p = 0.001) in the Swedish material, and decreased risk of PD (p = 2 x 10(-6)), with an odds ratio of 0.4 (95% CI 0.3-0.6) for heterozygous and 0.2 (95% CI 0.1-0.4) for homozygous carriers, in the Polish material. The identified haplotype includes a functional promoter haplotype previously associated with high transcriptional activity. Genetic variation in KEAP1 did not show any associations.ConclusionThese data suggest that variation in NFE2L2 modifies the Parkinson's disease process and provide another link between oxidative stress and neurodegeneration.
| S-EPMC2843602 | biostudies-literature
Project description:These studies profiled the expression of mRNAs and microRNAs (miRs) in lung neutrophils in WT mice during S. pneumoniae pneumonia and performed in depth in silico analyses. Lung neutrophils were isolated 24 hours after intratracheal instillation of PBS or S. pneumoniae, and mRNAs and miRs differentially expressed (DE) between S. pneumoniae- and PBS-treated samples were identified using microarrays.
2017-11-01 | GSE97920 | GEO