Pollutants and asthma: role of air toxics.

Asthma is a disease characterized by intermittent bronchoconstriction due to increased airway reactivity to both allergic and nonallergic stimuli. Most asthma exacerbations that result in hospitalization are associated with viral upper respiratory tract infections. Such infections typically induce T-helper type 1 (T(H)1) responses in the airway, involving activation of nuclear factor-kappaB (NF-Kappa B). However, a more recently appreciated cause of asthma exacerbation is exposure to pollutants, including ozone and various components of particulate matter (PM), including transition metals, diesel exhaust, and biologicals such as endotoxin. Although the role of air toxics in asthma pathogenesis remains incompletely examined, many components of PM that are active exacerbants of asthma are also prominent air toxics (metal ions and organic residues). These agents have been observed to activate NF-Kappa B. Reviewed in this article are the actions of specific air pollutants on airway inflammation in humans and potential common response pathways for ozone, PM, and several air toxics

Pollutants and asthma: role of air toxics.

Asthma is a disease characterized by intermittent bronchoconstriction due to increased airway reactivity to both allergic and nonallergic stimuli. Most asthma exacerbations that result in hospitalization are associated with viral upper respiratory tract infections. Such infections typically induce T-helper type 1 (T(H)1) responses in the airway, involving activation of nuclear factor-kappaB (NF-Kappa B). However, a more recently appreciated cause of asthma exacerbation is exposure to pollutants, including ozone and various components of particulate matter (PM), including transition metals, diesel exhaust, and biologicals such as endotoxin. Although the role of air toxics in asthma pathogenesis remains incompletely examined, many components of PM that are active exacerbants of asthma are also prominent air toxics (metal ions and organic residues). These agents have been observed to activate NF-Kappa B. Reviewed in this article are the actions of specific air pollutants on airway inflammation in humans and potential common response pathways for ozone, PM, and several air toxics

Environmental effects on immune responses in patients with atopy and asthma

Despite attempts and some successes to improve air quality over the decades, current U.S. national trends suggest that exposure to outdoor and indoor air pollution remains a significant risk factor for both the development of asthma and the triggering of asthma symptoms. Emerging science also suggests that environmental exposures during the prenatal period and early childhood years increase the risk of developing asthma. Multiple mechanisms mediate this risk as a wide range of deleterious air pollutants contribute to the pathogenesis of asthma, across a variety of complex asthma phenotypes. In this review, we will consider the role of altered innate and adaptive immune responses, gene by environment interactions, epigenetic regulation, and possibly gene by environment by epigene interactions. Gaining a greater understanding of the mechanisms that underlie the impact of exposure to air pollution on asthma, allergies, and other airway diseases can identify targets for therapy. Such interventions will include pollutant source reduction amongst those most exposed and most vulnerable, and novel pharmaceutical strategies to reduce asthma morbidity

Environmental determinants of allergy and asthma in early life

Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children

Flow cytometry of sputum: assessing inflammation and immune response elements in the bronchial airways

The evaluation of sputum leukocytes by flow cytometry is an opportunity to assess characteristics of cells residing in the central airways, yet it is hampered by certain inherent properties of sputum including mucus and large amounts of contaminating cells and debris

Nasal PMN response to repeated challenge with endotoxin in healthy volunteers

We have employed nasal challenge with lipopolysaccharide (LPS) followed by nasal lavage (NL) to experimentally induce and examine upper airway inflammation in human volunteers. It is unclear however whether adaptation within individuals occurs following repeated nasal challenge. This was a pilot study to determine if repeated nasal LPS challenge yields attenuation of markers of inflammation (primarily neutrophil response) in the NL fluid of healthy humans

Phosphorylation of p65 Is Required for Zinc Oxide Nanoparticle–Induced Interleukin 8 Expression in Human Bronchial Epithelial Cells

BackgroundExposure to zinc oxide (ZnO) in environmental and occupational settings causes acute pulmonary responses through the induction of proinflammatory mediators such as interleukin-8 (IL-8).ObjectiveWe investigated the effect of ZnO nanoparticles on IL-8 expression and the underlying mechanisms in human bronchial epithelial cells.MethodsWe determined IL-8 mRNA and protein expression in primary human bronchial epithelial cells and the BEAS-2B human bronchial epithelial cell line using reverse-transcriptase polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively. Transcriptional activity of IL-8 promoter and nuclear factor kappa B (NFκB) in ZnO-treated BEAS-2B cells was measured using transient gene transfection of the luciferase reporter construct with or without p65 constructs. Phosphorylation and degradation of IκBα, an inhibitor of NF-κB, and phosphorylation of p65 were detected using immunoblotting. Binding of p65 to the IL-8 promoter was examined using the chromatin immunoprecipitation assay.ResultsZnO exposure (2–8 μg/mL) increased IL-8 mRNA and protein expression. Inhibition of transcription with actinomycin D blocked ZnO-induced IL-8 expression, which was consistent with the observation that ZnO exposure increased IL-8 promoter reporter activity. Further study demonstrated that the κB-binding site in the IL-8 promoter was required for ZnO-induced IL-8 transcriptional activation. ZnO stimulation modestly elevated IκBα phosphorylation and degradation. Moreover, ZnO exposure also increased the binding of p65 to the IL-8 promoter and p65 phosphorylation at serines 276 and 536. Overexpression of p65 constructs mutated at serines 276 or 536 significantly reduced ZnO-induced increase in IL-8 promoter reporter activity.Conclusionp65 phosphorylation and IκBα phosphorylation and degradation are the primary mechanisms involved in ZnO nanoparticle-induced IL-8 expression in human bronchial epithelial cells

Src-Mediated EGF Receptor Activation Regulates Ozone-Induced Interleukin 8 Expression in Human Bronchial Epithelial Cells

Background:Human exposure to ozone (O3) results in pulmonary function decrements and airway inflammation. The mechanisms underlying these adverse effects remain unclear. Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of lung inflammation.ObjectiveWe examined the role of EGFR activation in O3-induced expression of the chemokine interleukin 8 (IL-8) in human bronchial epithelial cells (HBEC).MethodsWe detected phosphorylated EGFR using immunoblotting. EGFR dimerization was examined through cross-linking reaction and immunoblotting, and levels of IL-8 protein were measured using ELISA.ResultsExposure to O3 (0.25–1.0 ppm) induced rapid and marked increase in EGFR phosphorylation at the autophosphorylation site Y1068 and the transphosphorylation site Y845, implicating the involvement of Src kinase. Further investigation showed that O3 stimulation induced phosphorylation of Src at Y416, indicative of Src activation. Pharmacological inhibition of Src kinase activity abrogated O3-induced EGFR phosphorylation at tyrosines 1068 and 845. Moreover, pretreatment of BEAS-2B cells with inhibitor of either EGFR or Src kinase activities significantly blocked O3-induced IL-8 expression.ConclusionConclusion: O3 exposure increased IL-8 expression through Src-mediated EGFR transactivation in HBEC.Citation>Wu W, Wages PA, Devlin RB, Diaz-Sanchez D, Peden DB, Samet JM. 2015. Src-mediated EGF receptor activation regulates ozone-induced interleukin 8 expression in human bronchial epithelial cells. Environ Health Perspect 123:231–236; http://dx.doi.org/10.1289/ehp.130737

Attenuation of host defense function of lung phagocytes in young cystic fibrosis patients

Recent reports suggest that endotoxin exposure can blunt phagocyte functions. The aim of this study was to examine whether lung phagocytic cells have altered host defense function in young cystic fibrosis (CF) patients, and to explore the contribution of neutrophil elastase (NE) and surfactant proteins to these effects