Antagonistic effects of interferons(IFNs) and sodium orthovanadate on responses produced by TCDD in several culture systems
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- Antagonistic effects of interferons(IFNs) and sodium orthovanadate on responses produced by TCDD in several culture systems
- Hwan Mook Kim
- Bibliographic Citation
- Korean Journal of Toxicology, vol. 7, no. 2, pp. 239-255
- Publication Year
- Several types of IFNs were tested for their ability to suppress TCDD-inducible P-450 dependent mixed function oxidase (MFO) system in mouse primary hepatocytes. Mouse IFN-gamma (IFN-G) markedly suppress-ed EROD activity when added at the same time as TCDD (10 nM). The antagonism of EROD activity by IFN-G exhibited both a dose-(10-100 U/ml) and time-dependence. In contrast, mouse IFN-A/B ivas only moderately suppressive and on/v at high concentrations (500 U/ml). Rat IFN-G tuas even more selective than mouse, whereas human IFN-G had no activity. The species and subfype specificities were confirmed using a monoclonal Ab against mouse IFN-G, which blocked the action of mouse IFN-G, but had no effect on the suppression by either mouse IFN-A/B or rat IFN-G. To confirm the direct effect of IFN-G, liver parenchymal cells were isolated from crude liver cell preparation and it wqs found that purified parenchymal cells were still sensitive to effects of IFNs. These results indicate that IFNs, particularly IFN-G, can antagonize TCDD-mediated enzyme induction in primary hepatocytes similarly in immune system. Sodium orthovanadate was known as a selective inhibitor of phosphotyrosine phosphatase. In view of protein tyrosine phosphorylation, vanadate ivas tested in several cell culture systems. Vanadate markedly suppressed EROD activity when added at the same time as TCDD dose- and time-dependently in mouse primary hepatocytes. TCDD-induced inhibition of T-dependent antibody formation in mouse splenocytes was also reversed by sodium orthovanadate. As another system, human malaria culture system in human RBC was tested. In both synchronized and unsynchronized malaria parasites, TCDD showed a grovuth stimulation even though RBC did not have nucleus and Ah receptor dependent gene turn-on. Sod. orthovanadate also compensated TCDD-induced stimulation of malaria growth. By above results in three different culture model systems, it could be assumed that sodium orthouanadate act as a real antagonist against TCDD through a common mechanism with TCDD.
- Korea Soc-Assoc-Inst
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- 1. Journal Articles > Journal Articles
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