[Role of nuclear factor of kB in tumor necrosis factor alpha-mediated INS-1 cell apoptosis].
OBJECTIVE
To investigate the effect of cytokine tumor necrosis factor alpha(TNFalpha) on pancreatic beta cells apoptosis and the effect of transcription factor nuclear factor of kappa B (NF-kB) on TNFalpha-mediated apoptosis.


METHODS
INS-1 cells, a pancreatic beta cell line, were cultured,and recombinant DNA technique, transfection and reinfection technology were used to obtain INS-1/IkBDeltaN cells expressing inhibitor of kB (IkB)alphaDeltaN, mutant IkBalpha (inhibitor of NF-kB). DNA fragmentation assay and fluorescence analysis using a kB-luc reporter gene were applied to observe the NF-kB activity and beta cell apoptosis.


RESULTS
NF-kB activity induced by IL-Ibeta was detectable in INS-1 cells but not in INS-1/IkBDeltaN cells. After incubation of the cells with IL-1beta (10 micro g/L), TNFalpha (100 micro g/L) and interferon (IFN)gamma (100 000 U/L) for 48 hours, the combination of TNFalpha and IFNgamma induced apoptosis in INS-1 cells but not in INS-1/IkBDeltaN cells. No apoptosis was observed after incubation of INS-1 cells with IL-1beta or IFNgamma or IL-1beta plus IFNgamma.


CONCLUSIONS
Apoptosis is one of the TNFalpha-induced beta-cell death forms. NF-kB may play an important role in the TNFalpha-mediated beta-cell apoptosis. Inhibition of NF-kB activation protects beta-cells from TNFalpha-induced apoptosis.
Yang
Li-yong
LY
Department of Endocrinology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Yang
Yong-nian
YN
Chen
Zhi-jian
ZJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha