ABSTRACT
Survivin encoded by BIRC5 belongs to the group of proteins that inhibit apoptosis. It consists of the BIR and α-helical C domains. In addition to its inhibitory activity, it plays an important role in cell cycle regulation. Adalimumab is an immunosuppressive drug, a recombinant human anti-TNF-α monoclonal antibody. It is used in the treatment of autoimmune diseases.The aim of the study was to evaluate changes in the expression of BIRC5 and genes encoding apoptosis inhibitors (IAP), depending on the exposure time of the cells to adalimumab. The study material consisted of normal human dermal fibroblasts (NHDF) cultured under standard conditions in the presence of adalimumab (8µg/mL) for 2, 8 and 24 hours. The expression profile of genes associated with apoptosis was determined with the use of HG-U133A 2.0 oligonucleotide microarrays (Affymetrix). The comparative analysis was performed with one-way ANOVA and Tukey’s HSD tests (p<0.05) using the PL-Grid Infrastructure (http://www.plgrid.pl/en). In this study, it was determined that the number of mRNAs encoding proteins from the IAP family, differentiating the NHDF culture exposed to the anti-TNF drug from the control, varies depending on the exposure time of the cells to the drug (2h, 8h, 24h) and is as follows: 2h, 5 mRNAs; 8h, 6 mRNAs; 24h, 1 mRNAs. 1 ID mRNA changes its transcriptional activity regardless of the exposure time of cells to the drug and it is BIRC5 (p<0.05). The FC value for this mRNA is as follows: 2h vs. C, -1.59; 8h vs. C, -1.38; and 24h vs. C, 1.16. The effect of adalimumab on the transcriptional activity of the gene encoding survivin depends on the exposure time of the cells to the drug. BIRC5 is a gene differentiating the culture of normal human dermal fibroblasts regardless of the exposure time to adalimumab. The direction of expression change depends on the time of exposure to the drug.
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