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Enhanced IAP‐2 expression is critical for the resistance of endothelial cells to TNF‐α‐induced apoptosis
Author(s) -
Luo Jincai,
Shie JueLon,
Rana Jamal S.,
Wu Jiaping,
Wu Guifu,
Laham Roger J,
Li Jian
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb72
Subject(s) - apoptosis , tumor necrosis factor alpha , mapk/erk pathway , messenger rna , signal transduction , chemistry , microbiology and biotechnology , gene expression , biology , immunology , gene , biochemistry
This study is aimed to investigate the role of Inhibitor of Apoptotic Protein‐2 (IAP‐2), an anti‐apoptotic gene, in TNF‐α‐induced apoptosis in endothelial cells. Bovine aorta endothelial cells (BAEC) were treated with various growth factors and cytokines, and the expression of IAP‐2 mRNA was examined. TNF‐α strongly induced the expression of IAP‐2 mRNA in BAEC cells. The induction of IAP‐2 expression was dose‐dependent, starting from 0.5 ng/ml, increasing significantly at 10 ng/ml, and reaching a plateau at 50 ng/ml. Besides, the induction was also a time‐dependent response: after exposure to TNF‐α, IAP‐2 expression increased three‐folds at 3 hours and remained high at 24 hours (p< 0.001). Moreover, we found the expression of IAP‐2 induced by TNF‐α was enhanced at transcription level but not mRNA stability. To define signal pathways through which TNF‐α affects IAP‐2 expression, BAECs were pre‐treated with MAPK inhibitors followed by TNF‐α treatment. TNF‐α‐induced IAP‐2 mRNA expression was significantly blocked by both MEK and JNK inhibitors, accompanying increased number of apoptotic cells. Furthermore, TNF‐α‐induced apoptotic cells were dramatically suppressed when the expression of IAP‐2 was knocked down by the siRNA. In conclusion, our data demonstrate the up‐regulation of IAP‐2 expression is critical for the resistance of endothelial cells to TNF‐α‐induced apoptosis, mediated by MAPK and JNK signal pathways.