Ascorbic acid pre-treated quartz stimulates TNF-α release in RAW 264.7 murine macrophages through ROS production and membrane lipid peroxidation

摘要: Inhalation of crystalline silica induces a pulmonary fibrotic degeneration called silicosis caused by the inability alveolar macrophages to dissolve structure phagocytosed quartz particles. Ascorbic acid is capable partially dissolving crystals, leading an increase soluble concentration and generation new radical sites on surface. The reaction specific for forms silica. It has been already demonstrated increased cytotoxicity stronger induction pro-inflammatory cyclooxygenase-2 (COX-2) ascorbic pre-treated (QA) compared untreated (Q) in murine macrophage cell line RAW 264.7. Taking advantage enhanced response QA as Q particles, we investigated first steps activation contribution early signals generated directly from plasma membrane production TNF-α, cytokine that activates both inflammatory fibrogenic pathways. Here demonstrate TNF-α mRNA synthesis protein secretion are significantly 264.7 challenged with due intracellular ROS. Plasma membrane-particle contact, absence phagocytosis, sufficient trigger through mechanism involving lipid peroxidation this appears be even more detrimental survival than particle phagocytosis itself. Taken together these data suggest impairment i.e. case alcoholic subjects, could potentiate lung disease silica-exposed individuals.