Ascorbic acid-pretreated quartz enhances cyclo-oxygenase-2 expression in RAW 264.7 murine macrophages

Exposure to quartz particles induces a pathological process named silicosis.Alveolar macrophages initiate the disease through their activation, which isthe origin of the later dysfunctions. Ascorbic acid is known to selectivelydissolve the quartz surface. During the reaction, ascorbic acid progressivelydisappears and hydroxyl radicals are generated from the quartz surface.These observations may be relevant to mammalian quartz toxicity, as sub-stantial amounts of ascorbic acid are present in the lung epithelium. Westudied the inflammatory response of the murine macrophage cell lineRAW 264.7 incubated with ascorbic acid-treated quartz, through theexpression and activity of the enzyme cyclo-oxygenase-2 (COX-2). COX-2expression and prostaglandin secretion were enhanced in cells incubatedwith ascorbic acid-treated quartz. In contrast, no changes were observed incells incubated with Aerosil OX50, an amorphous form of silica. Quantifi-cation of COX-2 mRNA showed a threefold increase in cells incubatedwith ascorbic acid-treated quartz compared with controls. The transcriptionfactors, NF-kB, pCREB and AP-1, were all implicated in the increasedinflammatory response. Reactive oxygen species (H2O2and OH•) wereinvolved in COX-2 expression in this experimental model. Parallel experi-ments performed on rat alveolar macrophages from bronchoalveolar lavageconfirmed the enhanced COX-2 expression and activity in the cells incuba-ted with ascorbic acid-treated quartz compared with untreated quartz. Inconclusion, the selective interaction with, and modification of, quartz parti-cles by ascorbic acid may be a crucial event determining the inflammatoryresponse of macrophages, which may subsequently develop into acute inflammation, eventually leading to the chronic pulmonary disease silicosis.