Stable inhibition of NF-kappa B in salivary gland cells does not enhance sensitivity to TNF-alpha-induced apoptosis due to upregulation of TRAF-1 expression.
The transcription factor NF-kappa B inhibits the apoptotic response induced by TNF-alpha. However, in salivary gland cell clones (ACMT-6 and ACMT-7) in which NF-kappa B activation was suppressed by introduction of a super-repressor form of I kappa B-alpha cDNA, TNF-alpha did not cause apoptosis. Thus, to investigate the molecular mechanism involved in the unresponsiveness of these cell clones to TNF-alpha-induced apoptosis, we examined the effect of TNF-alpha on the expression of antiapoptotic proteins, including TNF receptor-associated factor (TRAF)-1, TRAF-2, cellular inhibitor of apoptosis protein (cIAP)-1, and cIAP-2. Here we show that expression of TRAF-1 was commonly detected by treatment with TNF-alpha in ACMT-6, ACMT-7, and an empty vector-transfected cell clone (ACpRc-1) and that downregulation of TRAF-1 protein by either treatment with an antisense oligonucleotide or introduction of an antisense plasmid resulted in the induction of apoptosis in these cell clones. Our results, therefore, suggest that one of the mechanisms by which cells acquire resistance to TNF-alpha-induced apoptosis is a TNF-alpha induction of TRAF-1.
Aota
Keiko
K
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3 Kuramoto-cho, Tokushima 770-8504, Japan. azumasa@dent.tokushima-u.ac.jp
Azuma
Masayuki
M
Tamatani
Tetsuya
T
Yamashita
Tsuyoshi
T
Ashida
Yuki
Y
Sato
Mitsunobu
M
D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002999:Clone Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D047990:TNF Receptor-Associated Factor 1; D015533:Transcriptional Activation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D011506:Proteins; D012333:RNA, Messenger; D047990:TNF Receptor-Associated Factor 1; D014409:Tumor Necrosis Factor-alpha