Protection of human islets from the effects of interleukin-1β by adenoviral gene transfer of an IκB repressor
Protection of human islets from the effects of interleukin-1β by adenoviral gene transfer of an IκB repressor
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DOI：
10.1074/jbc.m005943200
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发表时间：
2000-11-24
影响因子：
4.8
通讯作者：
Robbins, PD
中科院分区：
文献类型：
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作者：
Giannoukakis, N;Rudert, WA;Robbins, PD
白细胞介素-1 β (IL-1 β)是一种促炎细胞因子，可抑制β细胞功能并促进fas引发的细胞凋亡。IL-IP被认为在I型糖尿病患者胰腺细胞自身免疫破坏的早期起作用。IL-1 β通过激活NF-KB转录因子依赖的信号通路促进β细胞损伤。我们已经研究了β细胞是否可以通过过表达NF-kappaB活性抑制剂，通过腺病毒基因转移到培养的完整的人胰岛来保护β细胞免受IL-1 β的影响。用一种编码I κ b α非磷酸化、不可降解变体的腺病毒载体感染胰岛，在IL-1 β存在的情况下，导致胰岛素对葡萄糖的正常反应。此外，一氧化氮的产生被阻止，更重要的是，在I kappaB α基因转移后，fas引发的细胞凋亡被抑制。这些结果表明，阻断NF-KB通路可能会阻止细胞因子诱导的β细胞损伤，从而促进胰岛移植。
Interleukin-1 beta (IL-1 beta) is a pro-inflammatory cytokine that inhibits beta cell function and promotes Fas-triggered apoptosis. IL-IP is thought to act early in the initiation of the autoimmune destruction of pancreatic beta cells in type I diabetes. IL-1 beta promotes beta cell impairment, in part, by activating NF-KB transcription factor-dependent signaling pathways. We have examined whether beta cells could be protected from the effects of IL-1 beta by overexpressing an inhibitor of NF-kappaB activity, I kappaB alpha by adenoviral gene transfer to intact human islets in culture. Infection of islets with an adenoviral vector encoding a non-phosphorylatable, non-degradable variant of I kappaB alpha resulted in normal insulin responses to glucose in the presence of IL-1 beta. Furthermore, nitric oxide production was prevented and, more importantly, Fas-triggered apoptosis was inhibited following I kappaB alpha gene transfer. These results suggest that blocking the NF-KB pathway might prevent cytokine-induced beta cell impairment as a means of facilitating islet transplantation.