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KMID : 0371320090770050310
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Journal of the Korean Surgical Society
2009 Volume.77 No. 5 p.310 ~ p.319
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The Effect of FK506 to Generate Reactive Oxygen Species on T Lymphocyte Death
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Lee Ho-Kyun
Chung Sang-Young
Choi Soo-Jin-Na
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Abstract
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Purpose: Tacrolimus (FK506) has been widely used as an immunosuppressant in organ transplanted recipients to suppress organ rejection phenomenon. We investigated the role of oxidative stress and heme oxygense-1 by FK506 on human Jurkat T cells.
Methods: The cells viability was examined by DAPI stain, enzyme activity of caspase family proteins, and western blotting for Baks, PUMA, iNOS, HO-1. Cells were cultured in the absence or presence of CoPPIX or ZnPPIX and the fluorescence intensity was analyzed using a flow cytometry.
Results: Treatment with FK506 increased the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, and NO in Jurkat cells in a dose-dependent manner. Immunohistochemistry and Western blot analysis data revealed the hemoxygenase-1 (HO-1) was induced by the addition of FK506 in Jurkat cells. Induction of CoPP, HO-1 inducer, resulted in decreased intracellular H2O2 and NO concentrations. Instead ZnPP, an HO-1 competitive inhibitor did it reversely. In addition, ZnPP regulates iNOS protein synthesis by inhibition of HO-1.
Conclusion: Increase of HO-1 expression would induce to decrease the intracellular H2O2 and NO concentrations. Also, HO-1 would regulate iNOS protein synthesis. Consequently, we can expect the regulation of HO-1 expression with concomitants use of FK506 to suppress organ rejection phenomenon by enhancing apoptosis. (J Korean Surg Soc 2009;77:310-319)
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KEYWORD
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FK506, Reactive oxygen species, Heme Oxygenase-1
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