Transcriptome of lung epithelial cells stimulated by hemozoin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136007 | GEO | 2021/01/05
REPOSITORIES: GEO
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Project description:Transcriptome of lung epithelial cells stimulated by hemozoin
| PRJNA560929 | ENA
Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs.
2009-07-13 | GSE14751 | GEO
Project description:The role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-alpha). To gain insight into the common and specific effects of TNF-alpha and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-alpha (10ng/ml) or to hemozoin (12.5microgram/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-alpha were not affected by hemozoin. The genes modulated by TNF-alpha were significantly enriched for those encoding proteins involved in the control of type 1 interferon signalling and the immune response to viral infection. In contrast, genes induced by hemozoin were significantly enriched for functional roles in regulation of transcription and apoptosis. Further analyses by rtPCR revealed that hemozoin increases expression of transcription factors that form part of the integrated stress response which is accompanied by reduced expression of genes involved in DNA repair. This study confirms that hemozoin induces cellular stress on erythroblasts that is additional to and distinct from responses to inflammatory cytokines and identifies new genes that may be involved in the pathogenesis of severe malarial anemia. More generally the respective transcription profiles highlight the varied mechanisms through which erythropoiesis may be disrupted during infectious disease.
2015-02-04 | GSE65577 | GEO
Project description:The role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-alpha). To gain insight into the common and specific effects of TNF-alpha and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-alpha (10ng/ml) or to hemozoin (12.5microgram/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-alpha were not affected by hemozoin. The genes modulated by TNF-alpha were significantly enriched for those encoding proteins involved in the control of type 1 interferon signalling and the immune response to viral infection. In contrast, genes induced by hemozoin were significantly enriched for functional roles in regulation of transcription and apoptosis. Further analyses by rtPCR revealed that hemozoin increases expression of transcription factors that form part of the integrated stress response which is accompanied by reduced expression of genes involved in DNA repair. This study confirms that hemozoin induces cellular stress on erythroblasts that is additional to and distinct from responses to inflammatory cytokines and identifies new genes that may be involved in the pathogenesis of severe malarial anemia. More generally the respective transcription profiles highlight the varied mechanisms through which erythropoiesis may be disrupted during infectious disease. Erythroblasts derived from PBMCs were enriched to 97% purity for proerythroblast and intermediate/normoblast phases of differentiation using magnetic bead isolation. There were three treatment groups: media, P.falciparum hemozoin (12.5 microgram /ml hematin units) and tumour necrosis factor alpha(10ng/ml). Total RNA using 7.5 x105 cells per treatment from one donor was extracted using Trizol. Highly significant gene ontological findings (where p> x10^-17 but < x10^-7) were confirmed by quantitative PCR.
2015-02-04 | E-GEOD-65577 | biostudies-arrayexpress
Project description:Female mosquitoes, Anopheles gambiae, were injected with control-PBS or 200micrograms per ml hemozoin (sHz). Fat bodies were collected 24h post injection, before feeding. RNA was extracted and cDNA synthesized for microarray experiment. Three independent experiments (3x control and 3x sHz) arrays were performed. Fold change of genes expression in sHz-treated mosquitoes compared to PBS-treated ones was calculated. We aimed to describe how hemozoin activates the mosquito's immune system and which pathways are involved.
2016-04-08 | E-MTAB-1072 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-08 | GSE224162 | GEO
Project description:Hemozoin phagocytosis results in immunomodulation. This study was designed to explore gene expression responses to 15(S)-HETE in LPS-stimulated RAW 264.7 cells.
2009-12-17 | GSE15070 | GEO
Project description:We report that hemozoin nanocrystals demonstrate superparamagnetic properties, with direct measurements of the synthetic hemozoin magnetization. The results show that the magnetic permeability constant varies from μ = 4585 (at -20 °C) to 3843 (+20 °C), with the values corresponding to a superparamagnetic system. Similar results were obtained from the analysis of the diffusion separation of natural hemozoin nanocrystals in the magnetic field gradient, with μ = 6783 exceeding the value obtained in direct measurements by the factor of 1.8. This difference is interpreted in terms of structural differences between the synthetic and natural hemozoin. The ab initio analysis of the hemozoin elementary cell showed that the Fe(3+) ion is in the high-spin state (S = 5/2), while the exchange interaction between Fe(3+) electron-spin states was much stronger than kBT at room temperature. Thus, the spin dynamics of the neighboring Fe(3+) ions are strongly correlated, lending support to the superparamagnetism.
| S-EPMC4870585 | biostudies-other
Project description:Integrins are extracellular matrix receptors comprised of an a and b subunit that connect and mediate signaling between cells and the surrounding matrix. In organogenesis of epithelial tissues, the b1 integrin subunit regulates essential epithelial cell functions, but the role of b1 integrin in epithelial repair is poorly understood. To define the role of b1 integrin during alveolar repair, we challenged b1 integrin deficient mice with intratracheal lipopolysaccharide, resulting in increased mortality with emphysematous lungs 21 days following injury. The alveolar barrier was repopulated with an overabundance of type 2 alveolar epithelial cells, with reduced numbers of elongated alveolar type 1 cells, suggesting b1 integrin is required for type 2 to type 1 epithelial transition. Consistent with this finding, b1 deficient type 2 epithelial cells proliferated at increased rates throughout repair, lacked actin-rich cellular protrusions necessary for lateral cellular extension, and exhibited transcriptomic dysregulation of adherens junction and actin polymerization pathways. Finally, we show that b1 integrin balances actin polymerization versus stabilization through GTPase activation. Taken together, these data support a novel role for b1 integrin in re-establishing the alveolar niche after injury through modulation of type 2 epithelial cell proliferation and cytoskeletal-dependent cell shape change.
2023-06-10 | GSE205882 | GEO