title: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis.
abstract: Exposure to particulate silica (most crystalline polymorphs) causes a persistent inflammation sustained by the release of oxidants in the alveolar space. Reactive oxygen species (ROS), which include hydroxyl radical, superoxide anion, hydrogen peroxide, and singlet oxygen, are generated not only at the particle surface, but also by phagocytic cells attempting to digest the silica particle. Two distinct kinds of surface centers-silica-based surface radicals and poorly coordinated iron ions-generate O(2)(*)(-) and HO(*) in aqueous solution via different mechanisms. Crystalline silica is also a potent stimulant of the respiratory burst in phagocytic cells with increased oxygen consumption and production of O(*)(-), H(2)O(2), and NO leading to acute inflammation and HO(*) generation in the lung. Oxidative stress elicited by crystalline silica is also evidenced by increased expression of antioxidant enzymes such as manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase, and the enzyme inducible nitric oxide synthase (iNOS). Generation of oxidants by crystalline silica particles and by silica-activated cells results in cell and lung injury, activation of cell signaling pathways to include MAPK/ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) phosphorylation, increased expression of inflammatory cytokines (e.g., tumor necrosis factoralpha [TNFalpha], interleukin-1 [IL-1]), and activation of specific transcription factors (e.g., NFkappaB, AP-1). Silica can also initiate apoptosis in response to oxygen- and nitrogen-based free radicals, leading to mitochondrial dysfunction, increased gene expression of death receptors, and/or their ligands (TNFalpha, Fas ligand [FasL]).
authors.affiliation: Department of Chemistry IFM and Interdepartmental Center "G Scansetti" for Studies on Asbestos and other Toxic Particulates, University of Torino, Torino, Italy. bice.fubini@unito.it
authors.forename: Bice
authors.initials: B
authors.lastname: Fubini
authors.forename: Andrea
authors.initials: A
authors.lastname: Hubbard
mesh_terms: D000818:Animals; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000378:metabolism
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide