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  • Title: Molecular basis of interferon-gamma and lipopolysaccharide enhancement of phagocyte respiratory burst capability. Studies on the gene expression of several NADPH oxidase components.
    Author: Cassatella MA, Bazzoni F, Flynn RM, Dusi S, Trinchieri G, Rossi F.
    Journal: J Biol Chem; 1990 Nov 25; 265(33):20241-6. PubMed ID: 2173701.
    Abstract:
    In this study, we analyzed the expression of genes encoding for components of the phagocyte superoxide anion-generating system in human phagocytes treated with interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS). Human neutrophils express high levels of the 47-kDa cytosolic factor (p47-phox), which are down-regulated after treatment with IFN-gamma, but not with LPS. On the contrary, the steady-state levels of the heavy chain subunit of cytochrome b558 (gp91-phox) were increased by IFN-gamma and LPS in human monocyte-derived macrophages and neutrophils in a time- and dose-dependent fashion, whereas cytochrome b558 light chain subunit (p22-phox) mRNA was not influenced by either agent. Studies on post-transcriptional regulation at the level of mRNA stability indicate that, in neutrophils, IFN-gamma has no influence on gp91-phox and p47-phox mRNA half-lives. The content of the two cytochrome b558 subunits was quantified by enzyme-linked immunosorbent assay, which revealed that, in neutrophils, gp91-phox levels doubled after 4 h of treatment with IFN-gamma or LPS. Monocyte/macrophage maturation was associated with a gradual decrease in gp91-phox mRNA and protein levels, which were both restored by treatment with IFN-gamma for 24-48 h. These results suggest that induction of the gp91-phox gene and protein product by IFN-gamma or LPS is an important requirement in the mechanism of the enhancement of neutrophil and macrophage oxidative metabolism.
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