Transcription profiling of lungs from HeJ (TLR4 mutant) and OuJ (wild type) mice that have been exposed to ozone to study the molecular mechanisms underlying the effect of ozone on airways hyperpermability
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Eric Hoffman
PROVIDER: E-GEOD-476 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Ozone is a very common environmental pollutant and has been associated with the exacerbation of cardiopulmonary diseases like asthma. In this study the molecular mechanisms underlying the effect of ozone on airways hyperpermability were investigated. Two strains of mice, HeJ (Tlr4 mutant) and OuJ (wildtype) were exposed continuously to air or 0.3ppm of ozone. Lungs were removed and RNA was collected to generate expression profiles. Keywords: other
2003-07-16 | GSE476 | GEO
Project description:We previously identified toll-like receptor 4 (Tlr4) as a candidate gene responsible for ozone (O3)-induced pulmonary hyperpermeability and inflammation. The objective of this study was to determine the mechanism through which TLR4 modulates O3-induced pulmonary responses and to utilize transcriptomics to determine TLR4 effector molecules. C3H/HeJ (HeJ; Tlr4 mutant) and C3H/HeOuJ (OuJ; Tlr4 normal), mice were exposed continuously to 0.3 ppm O3 or filtered air for 6, 24, 48 or 72 hr. Affymetrix Mouse430A_MOE gene arrays were used to analyze lung homogenates from HeJ and OuJ mice followed using a bioinformatic analysis. Inflammation was assessed by bronchoalveolar lavage and molecular analysis by ELISA, immunoblotting, and transcription factor activity. TLR4 signals through both the MYD88-dependent and independent pathways in OuJ mice, which involves MAP kinase activation, NF-kappaB, AP-1, and KC. Microarray analyses identifiedTLR4 responsive genes for strain and time in OuJ versus HeJ mice (p<0.05). One significantly upregulated cluster of genes in OuJ were the heat shock proteins (Hspa1b; Hsp70), Hsp90ab1). Furthermore, O3-induced expression of HSP70 protein was increased in OuJ compared to HeJ mice following 24-48 h O3. Moreover, BAL polymorphonuclear leukocytes (PMN) and total protein were significantly reduced in response to O3 in Hspa1a/Hspa1btm1Dix (Hsp70-/-) compared to Hsp70+/+ mice (p<0.05). TLR4 signaling (MYD88-dependent), ERK1/2, AP-1 activity, and KC protein content were also significantly reduced after O3 exposure in Hsp70-/- compared to Hsp70+/+ mice (p<0.05). These studies suggest that HSP70 is involved in the regulation of O3-induced lung inflammation through the TLR4 pathway and provide evidence that HSP70 is an endogenous in vivo TLR4 ligand.
2012-02-29 | GSE20715 | GEO
Project description:Many Arabidopsis thaliana accession show sensitvity to the air pollutant ozone, including the accession Cvi-0 from the Cape Verde Islands. To understand and assist in genetic mapping of loci causing the ozone sensitvity of Cvi-0, transcript profiling was performed in Cvi-0, the tolerant Col-0, and a near isogenic line (Col-S) where ozone sensitivity was introgressesed from Cvi-0 to Col-0 through eight rounds of backcrossing.
2017-08-09 | GSE102363 | GEO
Project description:Ozone is a major air pollutant in highly populated areas. High levels of ambient ozone have been associated with decreased lung function and increased exacerbations of asthma in children and adults. However, the effects of ozone on the newborn’s lung are largely unknown. This study was aimed at profiling the newborn lung response to ozone at the transcriptome level to define the impact of ozone pollutant on the developing postnatal lung. Newborn mice were exposed to ozone or filtered normal air for 3 h. Total RNA was isolated from lung tissues at 6 and 24 h after completion of exposure and was subjected to gene expression analysis using Whole Mouse Genome Gene Expression 4X44K Microarrays (G2519F-014868, Agilent Technologies). Transcriptome analysis of the postnatal lung indicated that 455 genes were down-regulated and 166 genes were up-regulated by at least 1.5 fold at 6 h post-ozone exposure (t-test, p<0.05). At 24 h post exposure, 543 genes were down-regulated and 323 genes were up-regulated in the lungs of ozone-exposed newborn mice, compared to filtered air-exposed newborn mice (t-test, p<0.05). After controlling for false discovery rate, 50 genes were significantly down-regulated and only 4 genes were up-regulated at 24 h post ozone-exposure (q<0.05). Gene ontology enrichment analysis revealed that cell cycle-associated functions including cell division/proliferation, cellular assembly and organization were the predominant pathways negatively regulated by ozone exposure. These findings suggest that elevated ozone pollution may interfere with lung development and growth in the early age.
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Project description:Adiponectin is an adipose-derived hormone with anti-inflammatory activity. Following subacute ozone exposure (0.3 ppm for 24-72 h), pulmonary neutrophilic inflammation is augmented in adiponectin deficient mice. The purpose of this study was to use microarrays to examine the impact of adiponectin deficiency on changes in pulmonary gene expression induced by ozone, a common air pollutant.
2013-08-27 | GSE50183 | GEO
Project description:Ozone is a highly toxic air pollutant and global health concern. Mechanisms of genetic susceptibility to ozone-induced lung inflammation are not completely understood. We hypothesized Notch3 and Notch4 are important determinants of susceptibility to ozone-induced lung inflammation. Wild type (WT), Notch3 (Notch3-/-) and Notch4 (Notch4-/-) knockout mice were exposed to ozone (0.3 ppm) or filtered air for 6-72 hours. Ozone increased bronchoalveolar lavage fluid (BALF) protein, a marker of lung permeability, in all genotypes, but significantly greater concentrations were found in Notch4-/- compared to WT and Notch3-/-. Significantly greater mean numbers of BALF neutrophils were found in Notch3-/- and Notch4-/- mice compared to WT mice after ozone. Expression of whole lung Tnf was significantly increased after ozone in all genotypes, and was significantly greater in Notch3-/- mice compared to WT. Statistical analyses of the transcriptome identified differentially expressed gene networks between WT and knockout mice basally and after ozone, and included Trim30, a member of the inflammasome pathway, and Traf6, an inflammatory signaling member. These novel findings are consistent with Notch3 and Notch4 as susceptibility genes for ozone-induced lung injury, and suggest that Notch receptors protect against innate immune inflammation.
2015-02-24 | GSE58244 | GEO
Project description:Adiponectin is an adipose-derived hormone with anti-inflammatory activity. Following subacute ozone exposure (0.3 ppm for 24-72 h), pulmonary neutrophilic inflammation is augmented in adiponectin deficient mice. The purpose of this study was to use microarrays to examine the impact of adiponectin deficiency on changes in pulmonary gene expression induced by ozone, a common air pollutant. Lungs were harvested from wildtype and mice that were genetically deficient in adiponectin. Mice were exposed either to room air or to ozone (0.3 ppm) for 72 h. RNA was extracted and microarray analysis of gene expression performed. Both male and female mice were used.
2013-08-27 | E-GEOD-50183 | biostudies-arrayexpress
Project description:Ozone is a major air pollutant in highly populated areas. High levels of ambient ozone have been associated with decreased lung function and increased exacerbations of asthma in children and adults. However, the effects of ozone on the newbornM-bM-^@M-^Ys lung are largely unknown. This study was aimed at profiling the newborn lung response to ozone at the transcriptome level to define the impact of ozone pollutant on the developing postnatal lung. Newborn mice were exposed to ozone or filtered normal air for 3 h. Total RNA was isolated from lung tissues at 6 and 24 h after completion of exposure and was subjected to gene expression analysis using Whole Mouse Genome Gene Expression 4X44K Microarrays (G2519F-014868, Agilent Technologies). Transcriptome analysis of the postnatal lung indicated that 455 genes were down-regulated and 166 genes were up-regulated by at least 1.5 fold at 6 h post-ozone exposure (t-test, p<0.05). At 24 h post exposure, 543 genes were down-regulated and 323 genes were up-regulated in the lungs of ozone-exposed newborn mice, compared to filtered air-exposed newborn mice (t-test, p<0.05). After controlling for false discovery rate, 50 genes were significantly down-regulated and only 4 genes were up-regulated at 24 h post ozone-exposure (q<0.05). Gene ontology enrichment analysis revealed that cell cycle-associated functions including cell division/proliferation, cellular assembly and organization were the predominant pathways negatively regulated by ozone exposure. These findings suggest that elevated ozone pollution may interfere with lung development and growth in the early age. Three-day old BALB/c mice were exposed for 3 h to ozone (1000 parts per billion). Age-matching littermate controls were exposed for 3 h to filtered normal air. Whole lung tissue was collected 6 and 24 h after completion of exposure to ozone or filtered air and was subjected to microarray analysis. Each time point was performed separately with its own filtered air littermate controls. Pups were cross-fostered during exposure so that all pups were with a dam during exposure. A total of 6-8 mice were initially included in each group and time point. Of these, n=4 mouse lungs were randomly selected for use in gene expression analysis.
2014-03-12 | E-GEOD-45166 | biostudies-arrayexpress
Project description:Epigenetic alterations are a driving force of the carcinogenesis process. MicroRNAs play a role in silencing mutated oncogenes, thus defending the cell against the adverse consequences of genotoxic damages induced by environmental pollutants. These processes have been well investigated in lungs; however, although skin is directly exposed to a great variety of environmental pollutants, more research is needed to better understand the effect on cutaneous tissue. Therefore, we investigated microRNA alteration in human skin biopsies exposed to diesel fumes, ozone, and UV light for over 24 h of exposure. UV and ozone-induced microRNA alteration right after exposure, while the peak of their deregulations induced by diesel fumes was reached only at the end of the 24 h. Diesel fumes mainly altered microRNAs involved in the carcinogenesis process, ozone in apoptosis, and UV in DNA repair. Accordingly, each tested pollutant induced a specific pattern of microRNA alteration in skin related to the intrinsic mechanisms activated by the specific pollutant. These alterations, over a short time basis, reflect adaptive events aimed at defending the tissue against damages. Conversely, whenever environmental exposure lasts for a long time, the irreversible alteration of the microRNA machinery results in epigenetic damage contributing to the pathogenesis of inflammation, dysplasia, and cancer induced by environmental pollutants.
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Project description:Ozone is a highly toxic air pollutant and global health concern. Mechanisms of genetic susceptibility to ozone-induced lung inflammation are not completely understood. We hypothesized Notch3 and Notch4 are important determinants of susceptibility to ozone-induced lung inflammation. Wild type (WT), Notch3 (Notch3-/-) and Notch4 (Notch4-/-) knockout mice were exposed to ozone (0.3 ppm) or filtered air for 6-72 hours. Ozone increased bronchoalveolar lavage fluid (BALF) protein, a marker of lung permeability, in all genotypes, but significantly greater concentrations were found in Notch4-/- compared to WT and Notch3-/-. Significantly greater mean numbers of BALF neutrophils were found in Notch3-/- and Notch4-/- mice compared to WT mice after ozone. Expression of whole lung Tnf was significantly increased after ozone in all genotypes, and was significantly greater in Notch3-/- mice compared to WT. Statistical analyses of the transcriptome identified differentially expressed gene networks between WT and knockout mice basally and after ozone, and included Trim30, a member of the inflammasome pathway, and Traf6, an inflammatory signaling member. These novel findings are consistent with Notch3 and Notch4 as susceptibility genes for ozone-induced lung injury, and suggest that Notch receptors protect against innate immune inflammation. Wild-type, Notch3 knockout, and Notch4 knockout mice at 7-13 weeks of age were exposed continuously to air or 0.3 ppm ozone for 6, 24, or 48 hours. Three biological replicates from individual animals were included in each exposure group from each genotype and samples hybridized to the GeneChip Mouse Genome 430 2.0 array (Affymetrix).
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