Tumor necrosis factor -induced protein 8-like 1 promotes apoptosis by regulating B-cell leukemia/lymphoma-2 family proteins in RAW264.7 cells

Although the newly identified protein tumor necrosis factor -induced protein 8-like 1 (TNFAIP8L1), also known as TIPE1, has been reported to be able to induce apoptosis in human hepatocellular carcinoma cells, the involvement of TIPE1 in apoptosis remains to be elucidated. The present study investigated the pro-apoptotic effect of TIPE1 in an murine macrophage cell line, RAW264.7. The cell apoptosis rate was detected by flow cytometry. The results revealed that overexpressed TIPE1 could directly enhance the apoptosis and the cisplatin-induced cell death of RAW264.7 cells in vitro. Meanwhile, TIPE1 overexpression could suppress tumor growth in vivo. Furthermore, western blotting revealed that overexpressed TIPE1 could upregulate the expression of B-cell leukemia/lymphoma (Bcl)-2 associated X protein (Bax), Bcl-2 interacting killer (Bik) and p53 upregulated modulator of apoptosis (Puma), and activate the mitogen activated protein kinases (MAPKs) signaling pathway. However, western blotting demonstrated that inhibitors of the MAPKs pathway could not decrease the expression of Bax, Bik or Puma. These results indicated that TIPE1 could promote the apoptosis of RAW264.7 cells by upregulating the pro-apoptotic members of the Bcl-2 family of proteins, and that the MAPKs signaling pathway was not involved in the pro-apoptotic effect of TIPE1.