Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung inflammation induced by silica.

摘要: Exposure to mineral dusts such as silica has been associated with progressive pulmonary inflammation and fibrosis. There is evidence that the release of reactive oxygen intermediates (ROI) cytokines by alveolar macrophages (AM) involved in lung injury exposure. However, chronology relationship between these two mediators are poorly understood. In this study, an animal model silicosis used, allowing simultaneous follow-up histopathologic state, AM TNF-alpha production at protein (biologic assay) mRNA (reverse transcriptase-PCR) levels, ROI (luminol-dependent chemiluminescence), after bronchoalveolar lavages. particular, it shown intratracheal instillation (50 mg/kg) rats led fibrosis characterized cellular interstitial infiltrates granulomas, AM, 1) early continuous increase 12-O-tetradecanoylphorbol-13-acetate- or zymosan-triggered (days 1, 3, 14, 28 post-treatment), 2) a rise expression secretion on days 3 14. A free radical scavenger pretreatment (N-ter-butyl-alpha-phenylnitrone) reversed changes decreased level mRNA. These findings suggest important primary event determining silica-induced inflammatory process. may act autocrine paracrine manner regulate mechanism promoting gene expression. The critical role cytokine pathogenesis was confirmed anti-TNF-alpha Ab treatment.