title: Ascorbic acid-pretreated quartz enhances cyclo-oxygenase-2 expression in RAW 264.7 murine macrophages.
abstract: Exposure to quartz particles induces a pathological process named silicosis. Alveolar macrophages initiate the disease through their activation, which is the origin of the later dysfunctions. Ascorbic acid is known to selectively dissolve the quartz surface. During the reaction, ascorbic acid progressively disappears and hydroxyl radicals are generated from the quartz surface. These observations may be relevant to mammalian quartz toxicity, as substantial amounts of ascorbic acid are present in the lung epithelium. We studied the inflammatory response of the murine macrophage cell line RAW 264.7 incubated with ascorbic acid-treated quartz, through the expression and activity of the enzyme cyclo-oxygenase-2 (COX-2). COX-2 expression and prostaglandin secretion were enhanced in cells incubated with ascorbic acid-treated quartz. In contrast, no changes were observed in cells incubated with Aerosil OX50, an amorphous form of silica. Quantification of COX-2 mRNA showed a threefold increase in cells incubated with ascorbic acid-treated quartz compared with controls. The transcription factors, NF-kappaB, pCREB and AP-1, were all implicated in the increased inflammatory response. Reactive oxygen species (H(2)O(2) and OH(*)) were involved in COX-2 expression in this experimental model. Parallel experiments performed on rat alveolar macrophages from bronchoalveolar lavage confirmed the enhanced COX-2 expression and activity in the cells incubated with ascorbic acid-treated quartz compared with untreated quartz. In conclusion, the selective interaction with, and modification of, quartz particles by ascorbic acid may be a crucial event determining the inflammatory response of macrophages, which may subsequently develop into acute inflammation, eventually leading to the chronic pulmonary disease silicosis.
authors.affiliation: Advanced Biotechnology Center, Genoa, Italy. soniascarfi@unige.it
authors.forename: Sonia
authors.initials: S
authors.lastname: Scarfì
authors.forename: Umberto
authors.initials: U
authors.lastname: Benatti
authors.forename: Marina
authors.initials: M
authors.lastname: Pozzolini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Clavarino
authors.forename: Chiara
authors.initials: C
authors.lastname: Ferraris
authors.forename: Mirko
authors.initials: M
authors.lastname: Magnone
authors.forename: Laura
authors.initials: L
authors.lastname: Valisano
authors.forename: Marco
authors.initials: M
authors.lastname: Giovine
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011791:Quartz / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D011791:Quartz; D051546:Cyclooxygenase 2; D001205:Ascorbic Acid