Short course gamma tocopherol did not mitigate effects of ozone on airway inflammation in asthmatics.
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ABSTRACT:
SUBMITTER: Burbank AJ
PROVIDER: S-EPMC8015650 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Short course gamma tocopherol did not mitigate effects of ozone on airway inflammation in asthmatics.
Burbank Allison J AJ Hernandez Michelle L ML Robinette Carole C Wang Ting T Zhou Haibo H Alexis Neil N Bennett William D WD Peden David B DB
Inhalation toxicology 20200601 7
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Project description: Not available
| S-EPMC5632577 | biostudies-literature
Project description:BackgroundExposure to ozone (O3) is associated with increased risk of exacerbations of asthma, but the underlying mechanisms are not well studied.ObjectiveWe sought to determine whether O3 exposure would enhance airway inflammatory responses to allergen and the GSTM1-null genotype would modulate this enhancement.MethodsIn a crossover design, 10 asthmatic participants (5 with GSTM1-null genotype) who had specific sensitization to Dermatophagoides pteronyssinus (DP) were exposed to 160 ppb O3 or filtered air (FA) control for 4 hours on 2 separate days at least 3 weeks apart. At 20 hours after exposure, endobronchial challenge with DP allergen, and sham normal saline (NS) instillation, were performed in separate bronchi. Six hours later, a second bronchoscopy was performed to collect bronchoalveolar lavage (BAL) from the DP- and NS-challenged segments for analyses of inflammatory biomarkers. Linear regression compared cell and cytokine responses across the 4 exposure groups (FA-NS, O3-NS, FA-DP, O3-DP). Effect modification by GSTM1 genotype was assessed in stratified regressions.ResultsBAL eosinophil counts were increased in segments challenged with DP compared to sham-challenged segments (P < .01). DP challenge compared to sham also caused a significant increase in BAL concentrations of the TH2 cytokines IL-4, IL-5, IL-10, and IL-13 (P < .03 for all comparisons). O3 exposure did not significantly affect BAL cells or cytokine after DP challenge. Compared to GSTM1-present participants, GSTM1-null participants had significantly lower eosinophil (P < .041) and IL-4 (P < .014) responses to DP challenge after O3 exposure.ConclusionsWhile O3 did not cause a clear differential effect on airway inflammatory responses to allergen challenge, those responses did appear to be modulated by the antioxidant enzyme, GSTM1.
| S-EPMC9838882 | biostudies-literature
Project description:BackgroundAir pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation.ObjectiveThe objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans.MethodsThis was a randomized, placebo-controlled clinical trial testing the effect of a short course of γ-tocopherol-enriched supplementation on airway inflammation following a controlled exposure to wood smoke particulates.ResultsShort-course γ-tocopherol intervention did not reduce wood smoke-induced neutrophilic airway inflammation, but it did prevent wood smoke-induced eosinophilic airway inflammation.Conclusionγ-Tocopherol is a potential intervention for exacerbation of allergic airway inflammation, but further study examining longer dosing periods is required.
| S-EPMC10590746 | biostudies-literature
Project description:The ATP-binding cassette subfamily C member 4 gene encodes a transmembrane protein involved in the export of proinflammatory molecules, including leukotriene, prostaglandin, and sphingosine-1-phosphate across the plasma membrane. Those metabolites play important roles in asthma. We investigated the potential associations between ABCC4 gene polymorphisms and asthma phenotype. In total, 270 asthma patients and 120 normal healthy controls were enrolled for a genetic association study. Two polymorphisms (-1508A>G and -642C>G) in the ABCC4 promoter were genotyped. The functional variability of the promoter polymorphisms was analyzed by luciferase reporter assay. Inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. Serum and urinary eicosanoid metabolites, sphingosine-1-phosphate, were evaluated by quadrupole time-of-flight mass spectrometry. Asthma patients carrying the G allele at -1508A>G had significantly higher serum levels of periostin, myeloperoxidase, and urinary levels of 15-hydroxyeicosatetraenoic acid and sphingosine-1-phosphate (P = 0.016, P = 0.027, P = 0.032, and P = 0.010, resp.) compared with noncarrier asthma patients. Luciferase activity was significantly enhanced in human epithelial A549 cells harboring a construct containing the -1508G allele (P < 0.01 for each) compared with a construct containing the -1508A allele. A functional polymorphism in the ABCC4 promoter, -1508A>G, may increase extracellular 15-hydroxyeicosatetraenoic acid, sphingosine-1-phosphate, and periostin levels, contributing to airway inflammation in asthmatics.
| S-EPMC5474232 | biostudies-literature
Project description:BackgroundNitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO2 on inflammation without allergen exposure is poorly studied.ObjectivesWe investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics.MethodsNineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO2, 600 ppb NO2, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10-30 days before the first exposure.ResultsCompared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO2 (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO2 exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 (p = 0.001). Lung function, which was assessed daily, was not affected by NO2 exposure.ConclusionsWe observed that repeated peak exposures of NO2 performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner.
| S-EPMC4123022 | biostudies-literature
Project description:Inhaled ground level ozone (O3) has well described adverse health effects, which may be augmented in susceptible populations. While conditions, such as pre-existing respiratory disease, have been identified as factors enhancing susceptibility to O3-induced health effects, the potential for chemical interactions in the lung to sensitize populations to pollutant-induced responses has not yet been studied. In the airways, inhaled O3 reacts with lipids, such as cholesterol, to generate reactive and electrophilic oxysterol species, capable of causing cellular dysfunction and inflammation. The enzyme regulating the final step of cholesterol biosynthesis, 7-dehydrocholesterol reductase (DHCR7), converts 7-dehydrocholesterol (7-DHC) to cholesterol. Inhibition of DHCR7 increases the levels of 7-DHC, which is much more susceptible to oxidation than cholesterol. Chemical analysis established the capacity for a variety of small molecule antipsychotic drugs, like Aripiprazole (APZ), to inhibit DHCR7 and elevate circulating 7-DHC. Our results show that APZ and the known DHCR7 inhibitor, AY9944, increase 7-DHC levels in airway epithelial cells and potentiate O3-induced IL-6 and IL-8 expression and cytokine release. Targeted immune-related gene array analysis demonstrates that APZ significantly modified O3-induced expression of 16 genes, causing dysregulation in expression of genes associated with leukocyte recruitment and inflammatory response. Additionally, we find that APZ increases O3-induced IL-6 and IL-8 expression in human nasal epithelial cells from male but not female donors. Overall, the evidence we provide describes a novel molecular mechanism by which chemicals, such as APZ, that perturb cholesterol biosynthesis affect O3-induced biological responses.
| S-EPMC7053648 | biostudies-literature
Project description:BackgroundExposure to ozone (O₃) induces neutrophilic inflammation and goblet cell hyperplasia in humans and experimental animals. Because the solute carrier family 26-member 4 (Slc26a4; pendrin) gene induces mucin production and intraluminal acidification in the airways, it was hypothesized to be a key molecule in O₃-induced airway injury. Thus, we evaluated the role of Slc26a4 and the protective effects of ammonium chloride (NH₄Cl) in O₃-induced airway injury in mice.MethodsSix-week-old female BALB/c mice were exposed to filtered air or O₃ for 21 days (2 ppm for 3 hr/day). NH₄Cl (0, 0.1, 1, and 10 mM) was administered intratracheally into the airways. Airway resistance was measured using a flexiVent system, and bronchoalveolar lavage fluid (BALF) cells were differentially counted. Slc26a4 and Muc5ac proteins and mRNA were measured via western blotting, real-time polymerase chain reaction, and immunostaining. Tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, IL-1β, and caspase-1 were analyzed via western blotting.ResultsThe levels Slc26a4 protein and mRNA significantly increased in lung tissues from Day 7 to Day 21 of O₃ exposure, with concomitant increases in lung resistance, numbers of goblet cells in lung tissues, and inflammatory cells and thiocyanate (SCN-) levels in BALF in a time-dependent manner. Treatment with NH₄Cl significantly reduced these changes to levels similar to those of sham-treated mice, with a concomitant reduction of Slc26a4 proteins in lung lysates and SCN- levels in BALF. Slc26a4 protein was co-expressed with muc5ac protein in the bronchial epithelium, as indicated by immunofluorescence staining. NH₄Cl treatment also significantly attenuated the O₃-induced increases in IFN-γ, TNF-α, IL-17, IL-1β, and p20-activated caspase-1.ConclusionSlc26a4 may be involved in O₃-induced inflammatory and epithelial changes in the airways via activation of the inflammasome and the induction of IL-17 and IFN-γ. NH₄Cl shows a potential as a therapeutic agent for controlling O₃-induced airway inflammation and epithelial damage by modulating Slc26a4 expression.
| S-EPMC7431289 | biostudies-literature
Project description:PURPOSE:Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated. METHODS:Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay. RESULTS:The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (p < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (p < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (p < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (p < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (p = 0.095), and was negatively correlated with that of S. pneumoniae (p < 0.05). CONCLUSIONS:Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.
| S-EPMC7061157 | biostudies-literature
Project description:Background and aimsSevere asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided according to the eligibility criteria for one of the target biologic treatments.MethodsWe selected 91 severe asthmatics, uncontrolled despite high-dose ICS-LABA, and followed for >6 months with optimization of asthma treatment. Patients underwent clinical, functional and biological assessment, including induced sputum and nasal cytology. They were then clustered according to the eligibility criteria for omalizumab or mepolizumab/benralizumab.ResultsFour clusters were selected: A (eligible for omalizumab, n = 23), AB (both omalizumab and mepolizumab, n = 26), B (mepolizumab, n = 22) and C (non-eligible for both omalizumab and mepolizumab, n = 20). There was no difference among clusters for asthma control (Asthma Control Test and Asthma Control Questionnaire 7), pre-bronchodilator forced expiratory volume in 1 s, serum IgE and fractional exhaled nitric oxide levels. Sputum eosinophils were numerically higher in clusters AB and B, in agreement with the higher levels of blood eosinophils. Allergic rhinitis was more frequent in clusters A and AB, while chronic rhinosinusitis with nasal polyps prevalence increased progressively from A to C. Eosinophils in nasal cytology were higher in clusters AB, B and C.ConclusionEosinophilic upper and lower airway inflammation is present in the large majority of severe asthmatics, independently from the prescription criteria for the currently available biologics, and might suggest the use of anti-IL5/IL5R or anti IL4/13 also in patients without blood eosinophilia.The reviews of this paper are available via the supplemental material section.
| S-EPMC7716065 | biostudies-literature
Project description:Consumption of a high fat meal can increase neutrophilic airway inflammation in asthma subjects. This study investigates the molecular mechanisms driving airway neutrophilia following a high fat meal in asthmatics. Subjects with asthma (n = 11) and healthy controls (n = 8) consumed a high-fat/energy meal, containing total energy (TE) of 3846 kJ and 48 g of total fat (20.5 g saturated). Sputum was induced at 0 and 4 h, and gene expression was examined by microarray and quantitative real-time PCR (qPCR). Following the high fat dietary challenge, 168 entities were significantly differentially expressed greater than >1.5 fold in subjects with asthma, whereas, in healthy controls, only 14 entities were differentially expressed. Of the 168 genes that were changed in asthma, several biological processes were overrepresented, with 25 genes involved in "immune system processes". qPCR confirmed that S100P, S100A16, MAL and MUC1 were significantly increased in the asthma group post-meal. We also observed a strong correlation and a moderate correlation between the change in NLRP12 and S100A16 gene expression at 4 h compared to baseline, and the change in total and saturated non-esterified plasma fatty acid levels at 2 h compared to baseline. In summary, our data identifies differences in inflammatory gene expression that may contribute to increased airway neutrophilia following a high fat meal in subjects with asthma and may provide useful therapeutic targets for immunomodulation. This may be particularly relevant to obese asthmatics, who are habitually consuming diets with a high fat content.
| S-EPMC4728644 | biostudies-literature