title: The role of oxidative stress and innate immunity in O(3) and endotoxin-induced human allergic airway disease.
abstract: Ozone (O(3)) and endotoxin are common environmental contaminants that cause asthma exacerbation. These pollutants have similar phenotype response characteristics, including induction of neutrophilic inflammation, changes in airway macrophage immunophenotypes, and ability to enhance response to inhaled allergen. Evoked phenotyping studies of volunteers exposed to O(3) and endotoxin were used to identify the response characteristics of volunteers to these pollutants. New studies support the hypotheses that similar innate immune and oxidant processes modulate response to these agents. These include TLR4 and inflammasome-mediated signaling and cytokine production. Innate immune responses are also impacted by oxidative stress. It is likely that continued discovery of common molecular processes which modulate response to these pollutants will occur. Understanding the pathways that modulate response to pollutants will also allow for discovery of genetic and epigenetic factors that regulate response to these pollutants and determine risk of disease exacerbation. Additionally, defining the mechanisms of response will allow rational selection of interventions to examine. Interventions focused on inhibition of Toll-like receptor 4 and inflammasome represent promising new approaches to preventing pollutant-induced asthma exacerbations. Such interventions include specific inhibitors of innate immunity and antioxidant therapies designed to counter the effects of pollutants on cell signaling.
authors.affiliation: Division of Pediatric Allergy, Immunology, Rheumatology and Infectious Diseases, Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. peden@med.unc.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
mesh_terms: D000328:Adult; D000485:Allergens / Q000009:adverse effects / Q000276:immunology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D016207:Cytokines / Q000276:immunology; D004731:Endotoxins / Q000009:adverse effects* / Q000276:immunology; D057890:Epigenomics; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D058847:Inflammasomes / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress; D010126:Ozone / Q000009:adverse effects* / Q000276:immunology; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000975:Antioxidants; D016207:Cytokines; D004731:Endotoxins; D007166:Immunosuppressive Agents; D058847:Inflammasomes; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D010126:Ozone