The Effect of IFN- and TNF- on the NADPH Oxidase System of Human Colostrum Macrophages, Blood Monocytes, and THP-1 Cells

The aim of this work was to analyze the effect of Interferon(IFN) and tumor necrosis factor(TNF) on NADPH oxidase activity and gp91-phox gene expression in human colostrum macrophages (CM), peripheral blood monocytes (PBM), and myelomonocytic THP-1 cells. We also investigated the effect of IFNon the release of TNFby these cells. Our results show that under basal culture conditions, CM release more superoxide than PBM and THP-1 cells (p 0.05). The addition of IFN, alone or in combination with TNF, increased spontaneous superoxide release by PBM and THP-1 cells (p 0.05) and increased phorbol myristate acetate (PMA)-stimulated superoxide release by CM, PBM, and THP-1 cells (p 0.05). The NADPH oxidase activity of THP-1 cells consistently remained lower than that of CM or PBM, despite a dramatic response to IFNand TNF. Under basal conditions, gp91-phox gene expression was significantly higher in CM and PBM compared with THP-1 cells (p 0.05). The addition of IFNalone or in combination with TNFcaused a dramatic increase in gp91-phox gene expression in THP-1 cells (p 0.05) but not in CM or PBM. Under basal conditions or in the presence of IFN, CM released more TNFthan PBM or THP-1 cells (p 0.05). In addition, PBM released more TNFthan THP-1 cells (p 0.05). IFNdid not significantly augment the release of TNFby these cells (p 0.05). Thus, IFNand TNFinduced equivalent gp91-phox gene expression in THP-1 cells compared with CM or PBM but did not bring about equivalent NADPH oxidase activity. TNFrelease was higher in more mature cells. This partial divergence of gp91phox gene expression, NADPH oxidase activity, and TNFrelease is probably a consequence of different events of myeloid cell biology and relates at least in part to cell differentiation state.