title: Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms.
abstract: Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS) with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway. johan.ovrevik@fhi.no.
authors.forename: Johan
authors.initials: J
authors.lastname: Øvrevik
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway. magne.refsnes@fhi.no.
authors.forename: Magne
authors.initials: M
authors.lastname: Refsnes
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway. marit.lag@fhi.no.
authors.forename: Marit
authors.initials: M
authors.lastname: Låg
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway. jorn.holme@fhi.no.
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway. per.schwarze@fhi.no.
authors.forename: Per E
authors.initials: PE
authors.lastname: Schwarze
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000378:metabolism*; D052638:Particulate Matter / Q000378:metabolism / Q000633:toxicity*; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
chemical_list: D016877:Oxidants; D052638:Particulate Matter
keywords: ROS; asbestos; cytokines; fibers; inflammasome; nanoparticles; oxidants; particles; particulate matter; quartz; receptors; silica; transcription factors