Intracellular glutathione redox status modulates MCP-1 expression in pulmonary granulomatous vasculitis.

摘要: A wide spectrum of human lung diseases is characterized by the presence granulomas. Although understanding pathways leading to their development remains incomplete, data from in vitro studies suggest that neutrophils, monocytes, and secreted products (eg, hydrogen peroxide, H2O2) influence pathogenesis pulmonary granulomatous disease through regulation local chemokine cytokine production. Using a well-characterized rat model glucan-induced vasculitis, we sought determine role intracellular glutathione (GSH) redox status expression monocyte chemoattractant protein-1 (MCP-1). Previous have revealed vascular wall MCP-1 obligatory for granuloma both neutrophils peroxide are required induction. Because part mediated redox-sensitive transcription factors nuclear factor-kappa B (NF-kappaB) activator (AP-1), studied activation as function varying GSH granulomatosis. Infusion particulate yeast cell glucan into rats resulted rapid decrease concentrations which was accompanied NF-kappaB AP-1. The pattern AP-1 turn correlated temporally with MCP-1. Administration L-buthionine-S, R-sulfoximine, specific inhibitor gamma-glutamyl cysteine synthetase, significant reduction pools. depletion more than 100% increase increased cytosolic translocation while having no effect on levels. These observations disease, modulates factors.