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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effect of interferons on P-glycoprotein-mediated rhodamine-123 efflux in cultured rat hepatocytes.

The effect of interferon (IFN)-beta and IFN-gamma on P-glycoprotein (P-gp)-mediated efflux of rhodamin-123(Rho-123), a typical substrate of P-gp, was studied in rat hepatocytes in primary culture. After treatment with IFN-beta, IFN-gamma, or both for 3 days, steady-state levels of Rho-123, incorporated into the hepatocytes, were measured to evaluate the P-gp activity. Whereas IFN-beta did not affect the intracellular level of Rho-123, IFN-gamma treatment caused a significant increase of the level, suggesting that IFN-gamma treatment suppresses the expression of P-gp or its activity. A combination of the two types of IFN exhibited a similar effect to that of IFN-gamma alone. The effect of IFN-gamma was still observed in the presence of H(2)O(2), which enhances the expression and activity of P-gp. Immunoblot analysis using a monoclonal antibody C219 revealed, however, that P-gp expression was increased after treatment with IFN-gamma, but only slightly by IFN-beta treatment. These results suggest that the enhanced Rho-123 uptake of rat primary hepatocytes induced by IFN-gamma does not result from reduced expression of P-gp but, rather, from impaired maturation or dysfunction of the efflux transporter.[1]

References

  1. Effect of interferons on P-glycoprotein-mediated rhodamine-123 efflux in cultured rat hepatocytes. Akazawa, Y., Kawaguchi, H., Funahashi, M., Watanabe, Y., Yamaoka, K., Hashida, M., Takakura, Y. Journal of pharmaceutical sciences. (2002) [Pubmed]
 
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