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KMID : 0613820170270080873
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Journal of Life Science
2017 Volume.27 No. 8 p.873 ~ p.878
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Inhibitory Effect of NAD(P)H:Quinone Oxidoreductase 1 on the Activation of Macrophages
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Hong Ji
Zhang Peng
Yoon I-Na
Kim Ho
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Abstract
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We previously reported that NAD(P)H:quinone oxidoreductase 1 (NQO1)-knockout (KO) mice exhibited spontaneous inflammation in the gut. We also found that NQO1-KO mice showed highly increased inflammatory responses compared with NQO1-WT control mice when subjected to DSS-induced experimental colitis. In a Clostridium difficile toxin-induced mouse enteritis model, NQO1-KO mice were also sensitive compared with NQO1-WT mice. Moreover, numerous studies have shown that NQO1 is functionally associated with immune regulation. Here, we assessed whether NQO1 defects can alter macrophage activation. We found that peritoneal macrophages isolated from NQO1-KO mice produced more IL-6 and TNF-a than those isolated from NQO1-WT mice. Moreover, the dicumarol-induced inhibition of NQO1 significantly increased IL-6 and TNF-a production in peritoneal macrophages isolated from NQO1-WT mice, as well as in the cultured mouse macrophage cell line, RAW264.7. These results indicate that NQO1 may negatively regulate the activation of macrophages. Knockout or chemical inhibition of NQO1 markedly reduced the expression of IκB (inhibitor of NFκB) in both mouse peritoneal macrophages and RAW264.7 cells. Finally, RAW264.7 cells treated with dicumarol exhibited morphological changes reflecting macrophage activation. Our results suggest that NQO1 may suppress the NFkB pathways in macrophages, thereby suppressing the activation of these cells. Thus, immunosuppressive activity may be among the many possible functions of NQO1.
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KEYWORD
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Immunosuppression, IL-6, macrophage, NQO1, TNF-α
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