【Animal Modeling】-Tumor necrosis factor-α-induced protein-8-like molecule 2 promotes apoptosis of CD4-positive T cells in heat-injured mice

  Objective: To investigate the effect of tumor necrosis factor-α-induced protein-8-like molecule 2 (TIPE2) on apoptosis of spleen CD4+ T lymphocytes in a mouse model of severe scald.

  Methods: 140 adult male BALB/C mice were divided into 6 groups, siTIPE2/overexpressing lentivirus was produced by small RNA interference technology, and the mouse model of severe scald was replicated. The spleen CD4+ T cells of BALB/c mice were isolated, and the apoptosis of CD4+ T lymphocytes in each group, Smad2/Smad3, phospho(P)-Smad2/P-Smad3 and B-lymphoma-2 (Bcl-2) family were detected Expression of the protein Bcl-2/Bim. The changes of mitochondrial membrane potential and cytochrome C in CD4+T of mice in each group and the cysteine-containing aspartate proteolytic enzymes (caspase-3) and (caspase-3) in CD4+T of mice in each group were detected. -8), (caspase-9) activation.

  Results: The apoptosis rate of CD4+ T lymphocytes in the siTIPE2-burn group was 12.33%, which was lower than that in the other groups except the sham group, and the protein expression (gray value) of P-smad2/P-Smad3 was significantly decreased (P<0.01). The protein expression of Bcl-2 in the siTIPE2-burn group was higher than that in the other groups (P<0.05), while the expression of Bim was decreased (P<0.05). The level of mitochondrial membrane potential cytochrome C in siTIPE2-burn group was lower than that in other groups except sham group (P<0.05). The remaining groups decreased (P<0.05). The TIPE2-burn group had the highest apoptotic rate, the TIPE2-burn group had a significantly higher protein expression of Smad2/Smad3 than the sham group (P<0.05), and the P-smad2/P-Smad3 protein expression was significantly higher than that of the other groups (P<0.05). ; The mitochondrial membrane potential in CD4+T was lower than the other groups (P<0.01), the level of cytochrome C was increased, and the activities of caspase-3, caspase-8 and caspase-9 were increased compared with other groups (P<0.05).

  Conclusion: TIPE2, as an important negative regulatory molecule, can accelerate T lymphocyte apoptosis by promoting transforming growth factor β (TGF-β/Smads signaling pathway and mitochondria-related apoptosis pathway).