title: Antioxidant treatment attenuates cytokine and chemokine levels in murine macrophages following silica exposure.
abstract: Alveolar macrophages play a key role in the development of silicosis by releasing a host of mediators, such as, cytokines and chemokines, which contribute to a complex network of interactions that result in the onset of lung injury, inflammation, and potentially fibrosis. Using a murine macrophage cell line, RAW 264.7, we exposed the cells to cristobalite-silica (35 micrograms/cm(2)) in the presence or absence of antioxidants and various modifiers of cellular antioxidant status. Treatment with dimethyl sulfoxide, extracellular glutathione, or N-acetyl-L-cysteine (NAC) decreased cristobalite-induced tumor necrosis factor (TNF)-alpha mRNA levels by 40%, 20%, and 42%, respectively. TNF-alpha protein levels were decreased by 90%, 32%, and 53%, respectively. Cristobalite-induced macrophage inflammatory protein (MIP)-2 mRNA levels were reduced by 52%, 38%, and 57%, with DMSO, GSH, and NAC treatment, respectively. Both MIP-1alpha and MIP-1beta mRNA levels were reduced at a magnitude similar to the reduction in TNF-alpha mRNA levels, whereas monocyte chemotactic protein (MCP)-1 mRNA levels were reduced at a magnitude similar to the reduction in MIP-2 mRNA levels following antioxidant treatment. These results suggests that the macrophage response to cristobalite exposure is mediated at least in part by oxidant stress.
authors.affiliation: Departments of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, 14642, USA.
authors.forename: E G
authors.initials: EG
authors.lastname: Barrett
authors.forename: C
authors.initials: C
authors.lastname: Johnston
authors.forename: G
authors.initials: G
authors.lastname: Oberdörster
authors.forename: J N
authors.initials: JN
authors.lastname: Finkelstein
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D012260:Ribonucleases / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000931:Antidotes; D000975:Antioxidants; D018925:Chemokines; D016207:Cytokines; D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase; D012260:Ribonucleases; D005978:Glutathione; D000111:Acetylcysteine; D004121:Dimethyl Sulfoxide