Cooperative effects of interferon-γ on the induction of NADPH oxidase by retinoic acid or 1, 25 (OH) 2-vitamin D3 in monocytic U937 cells

H Obermeier, A Sellmayer, U Danesch… - … et Biophysica Acta (BBA …, 1995 - Elsevier
H Obermeier, A Sellmayer, U Danesch, M Aepfelbacher
Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1995Elsevier
The effect of retinoic acid (RA), 1, 25-dihydroxyvitamin D3 (1, 25-D3) or human recombinant
interferon-γ (IFN-γ) on the induction of NADPH oxidase was studied in premonocytic U937
cells. Differentiation with the combination of either RA (1 μM) or 1, 25-D3 (10 nM) with IFN-γ
(100 IU/ml) induced NADPH oxidase activity as demonstrated by increased superoxide
anion (O2−) generation in response to stimulation with phorbol myristate acetate (PMA, 100
nM). Induction of NADPH oxidase activity was preceded by increases in mRNA levels of p47 …
The effect of retinoic acid (RA), 1,25-dihydroxyvitamin D3 (1,25-D3) or human recombinant interferon-γ (IFN-γ) on the induction of NADPH oxidase was studied in premonocytic U937 cells. Differentiation with the combination of either RA (1 μM) or 1,25-D3 (10 nM) with IFN-γ (100 IU/ml) induced NADPH oxidase activity as demonstrated by increased superoxide anion (O2) generation in response to stimulation with phorbol myristate acetate (PMA, 100 nM). Induction of NADPH oxidase activity was preceded by increases in mRNA levels of p47-phox, p67-phox and gp91-phox, which encode three subunits of the enzyme, and immunoblot analysis of the p47-phox and p67-phox proteins revealed that the increases in mRNA levels were equally reflected by increases in protein levels. In contrast, RA, 1,25-D3 or IFN-γ alone did not induce NADPH oxidase activity which correlated with their failure to increase p67-phox and gp91-phox mRNA levels. The mRNA of p21 racl, a GTP-binding protein that regulates NADPH oxidase activity in macrophages, was constitutively expressed in undifferentiated cells and was not affected by differentiation. These data indicate that induction of a functional NADPH oxidase in premonocytic U937 cells requires the cooperative actions of IFN-γ plus RA or 1,25-D3 and is reflected in the increased expression of p67-phox and gp91-phox.
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