The microbiome contributes to obesity-related increases in the pulmonary response to ozone
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ABSTRACT:
PROVIDER: PRJEB30674 | ENA |
REPOSITORIES: ENA
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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:Rationale: Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases TLR4-mediated response to subsequent stimulation with lipopolysaccharide (LPS). To further explore the pulmonary innate immune response to ozone exposure, we investigated the effect of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Methods: Bronchoalveolar lavage (BAL) and lungs were harvested from C57Bl/6 mice after exposure to ozone or filtered air followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the BAL, surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. Results: We demonstrate an increased BAL cell influx, increased IL-6 and KC, and decreased MIP-1α and TNF-α in response to Pam3CYS as a result of ozone pre-exposure. We also observed increased cell surface expression of TLR4, TLR2 and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in expression of genes related to injury repair and cell cycle as a result of ozone exposure. When comparing Pam3CYS treated animals to saline treated animals with or without ozone, genes associated with inflammation were significantly increased. Potentially novel ozone exposure candidate genes (CCK, RELM-α and β) were identified. Conclusion: Our results extend previous findings with ozone/LPS to other TLRs PAMPs and suggest that ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level.
2012-08-01 | GSE38014 | 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:Rationale: Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases TLR4-mediated response to subsequent stimulation with lipopolysaccharide (LPS). To further explore the pulmonary innate immune response to ozone exposure, we investigated the effect of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Methods: Bronchoalveolar lavage (BAL) and lungs were harvested from C57Bl/6 mice after exposure to ozone or filtered air followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the BAL, surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. Results: We demonstrate an increased BAL cell influx, increased IL-6 and KC, and decreased MIP-1α and TNF-α in response to Pam3CYS as a result of ozone pre-exposure. We also observed increased cell surface expression of TLR4, TLR2 and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in expression of genes related to injury repair and cell cycle as a result of ozone exposure. When comparing Pam3CYS treated animals to saline treated animals with or without ozone, genes associated with inflammation were significantly increased. Potentially novel ozone exposure candidate genes (CCK, RELM-α and β) were identified. Conclusion: Our results extend previous findings with ozone/LPS to other TLRs PAMPs and suggest that ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level. Mice were exposed to either 2ppm ozone or filtered air (FA) for 3 hours. 24 hours following ozone exposure, mice from either the ozone or FA group were treated intratracheally with either 100ug of Pam3CYS in saline or saline alone. Animals were euthanized 4 or 24 hours post-Pam3CYS exposure. RNA from whole lung tissue from 4 animals per group was profiled.
2012-07-31 | E-GEOD-38014 | biostudies-arrayexpress
Project description:The microbiome contributes to obesity-related increases in the pulmonary response to ozone
| PRJDB7902 | ENA
Project description:Ozone and allergen inhalation causes pulmonary inflammation and impairs lung function in mice. These effects are heightened in the absence of the immunosuppressive surfactant protein-D. Increased expression of inflammatory mediators is critical for the initiation of inflammation and impairment of lung function following ozone and allergen inhalation. An Affymetrix microarray was used to understand global changes in gene expression that occurred after ozone inhalation and/or allergen sensitization and challenge in the abscence of surfactant protein-D. Identification of the set of genes up and down regulated in response to ozone and/or allergen led us to study specific cellular inflammatory pathways. This study has important implications for the study of lung diseases like asthma.
2019-04-30 | GSE111155 | GEO
Project description:Fish oil, olive oil, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they can protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet enriched with fish, olive, or coconut oil starting at 4 weeks of age for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4h/day for 2 consecutive days. The fish oil diet completely abolished phenylephrine-induced vasoconstriction that was increased following ozone exposure in the animals fed all other diets. Only the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors in the lung. Serum miRNA profile was assessed using small RNA-sequencing in normal and fish oil groups and demonstrated marked depletion of a variety of miRNAs, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that while fish oil offered protection from ozone-induced aortic vasoconstriction, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective dietary supplement.
2018-01-11 | GSE102015 | GEO
Project description:Ozone is a common pollutant and a potent oxidant in industrialized nations. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose binding lectin (MBL), which has a central role in the activation of the complement pathway of innate immunity, is a necessary component of the pro-inflammatory events caused by ozone-mediated activation of the innate immune system. Wild-type (Mbl+/+) and MBL deficient (Mbl-/-) mice were exposed to ozone (0.3 ppm) for 24, 48, and 72 hours, and bronchoalveolar lavage fluid (BALF) was examined for inflammatory markers. Compared to Mbl+/+ mice, significantly greater mean BALF eosinophils, neutrophils and neutrophil attractants CXCL2 (MIP-2) and CXCL5 (LIX) were found in Mbl-/- mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in expression response profiles and networks at baseline (e.g. NRF2 mediated oxidative stress response) and after exposure (e.g. humoral immune response) between Mbl+/+ and Mbl-/- mice. The microarray data were further analyzed using a pattern recognition analysis for Extracting Patterns and Identifying co-expressed Genes (EPIG), and discovered several informative differential response patterns and subsequent gene sets, including antimicrobial response and inflammatory response. These novel findings demonstrate that targeted deletion of Mbl caused differential expression of inflammation-related gene sets basally and after exposure to ozone, and significantly reduced pulmonary inflammation thus indicating an important innate immunomodulatory role of the gene in this model.
2016-04-25 | GSE68522 | GEO
Project description:Obesity exacerbates inflammation upon lung injury; however, the mechanisms by which obesity primes pulmonary dysregulation prior to injury are not well studied. Notably, little is known about how obesity dysregulates pulmonary polyunsaturated fatty acid (PUFA) metabolism that is central to inflammation initiation and resolution. Herein, we first show that a high fat diet (HFD) administered to C57BL/6J mice increases the relative abundance of pulmonary PUFA-containing triglycerides and the concentration of PUFA-derived oxylipins, independent of an increase in total pulmonary PUFAs, prior to onset of pulmonary inflammation. Experiments with a genetic model of obesity did not recapitulate the effects of the HFD on the pulmonary oxylipin signature, revealing a diet-driven effect. Subsequent pulmonary next-generation RNA sequencing identified complex and unique transcriptional regulation with the HFD. The HFD increased pathways related to glycerophospholipid metabolism and immunity, including an elevation in B cell differentiation and signaling. Finally, computational integration of lipidomic with transcriptomic data revealed novel HFD-driven networks between glycerophospholipid metabolism and B cell receptor signaling with specific PUFA-derived oxylipins. Collectively, these data show obesity dysregulates pulmonary PUFA metabolism prior to lung injury, which may be a mechanism by which obesity primes the lungs to respond poorly upon infectious and/or inflammatory challenges.
2022-09-28 | GSE194403 | GEO
Project description:Ozone-induced lung injury/inflammation and pulmonary/hypothalamus gene expression are diminished in adrenalectomized (ADREX) rats. Acute ozone exposure induces metabolic alterations concomitant with increases in epinephrine and corticosterone. We hypothesized that adrenal hormones are responsible for observed hepatic ozone effects, and in ADREX rats, these changes would be diminished. Five-seven days after sham or ADREX surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4-hrs. Serum samples were analyzed for metabolites and liver for transcriptional changes immediately post-exposure. Ozone increased circulating triglycerides, cholesterol, free fatty acids, and leptin in sham but not ADREX rats. Ozone-induced inhibition of glucose-mediated insulin release was reversed in ADREX rats. Unlike diminution of hypothalamus and lung mRNA expression changes, ADREX in air-exposed rats (ADREX-air/sham-air) caused differential expression of ~1000 genes in liver. Likewise, ~1000 genes were differentially expressed in ozone-exposed ADREX rats (ADREX-ozone/ADREX-air). Ozone-induced hepatic changes in sham rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified significant similarity to glucocorticoids and pathways involving CREBBP. These changes were absent in ADREX rats exposed to ozone. However, ozone caused unique changes in ADREX liver mRNA reflecting activation of synaptogenesis, neurovascular coupling, neuroinflammation, and insulin signaling with inhibition of senescence pathways. In these rats, upstream predictor analysis identified numerous microRNAs involved under glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and the need for further research elucidating their role in propagating environmentally driven diseases.
2022-11-02 | GSE196818 | GEO