The Interference of Cytokine Expressions in Inducible Antizyme Tet-On Jurkat T Cell System

• Main Authors: Hsiu-Hsueh Tseng, 曾秀學
• Other Authors: 高銘欽
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/67322811606527779495

碩士 === 中國醫藥大學 === 醫學研究所 === 96 === Antizyme (AZ) directly binds ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis, and inactivates and degrades ODC by the 26S proteasome without ubiquitination. The production of full-length functional AZ protein depends on polyamine levels and AZ gene requires +1 translational frameshifting. However, the delicately cellular function of AZ is still unidentified. Mammalian cells in response to various stimuli such as double-stranded RNAs or viral infection can stimulate the induction of interferons (IFNs). In most viral infections, T cells can be induced to activate, differentiate and produce a number of cytokines that defend against viruses. Previous studies have shown the antiviral and antiproliferative effects of IFNs are mediated by the 2’-5’oligoadenylate RNase L RNA decay pathway. Recently, this pathway is confirmed to increase translational readthrough efficiency at premature termination codons and increase +1 frameshift efficiency at the AZ +1 frameshift site. To elucidate the role of full-length functional AZ in T cell activation, we examined whether conditional expression of full-length AZ protein could elucidate the hallmarks of Jurkat T cell activation. Using Jurkat Tet-On System, AZ overexpression was found to affect the expression of cytokines, especially the cytokines of immuno-activation, including IL-2, IL-4, IL-5, IL-12 (p40) and IFN-γ. The specific activation of IL-2 is a pivotal cytokine in Jurkat T cell activation. This study demonstrated that AZ-triggered expression of IL-2 might be through the transcriptional modulation of IL-2 gene. Further analysis on the signaling transduction revealed that phosphorylation of IKKα/β and IκB-α were increased, total IκB-α was degraded and the nuclear translocation of NF-κB was moderately increased at early stage of activation after AZ induction. Taken together, we suggest that AZ may own the capacity of immuno-regulation and influence IL-2 expression to regulate T lymphocyte surveillance and activation.