Zhao Yuxing, Krishnamurthy Balasubramanian, Mollah Zia U A, Kay Thomas W H, Thomas Helen E
St Vincent's Institute, 41 Victoria Parade, Fitzroy, Victoria 3065, Melbourne, Australia.
Inflamm Allergy Drug Targets. 2011 Jun;10(3):208-17. doi: 10.2174/187152811795564046.
Type 1 diabetes is an autoimmune disease in which pancreatic beta cells are destroyed by autoreactive T cells. It is a common pediatric disease with increasing incidence. Islet transplantation may be a therapeutic option, however, the current limitations of this procedure mean that for most sufferers of type 1 diabetes there is no cure. The transcription factor NF-κB has been widely studied for its role in development of type 1 diabetes. Recent data have shown that NF-κB is required for activation of autoreactive T cells, and its hyperactivity in monocytes and dendritic cells results in altered cytokine secretion and antigen presentation, which ultimately contributes to the initiation of type 1 diabetes. NF-κB is also activated by a number of proinflammatory cytokines to regulate both the survival and death of beta cells. The critical role of NF-κB in type 1 diabetes renders it a promising pharmaceutical target in the intervention of this disease and further understanding of the NF-κB pathway will have an important implication on the development of novel and safe therapeutic strategies.
1型糖尿病是一种自身免疫性疾病,其中胰腺β细胞被自身反应性T细胞破坏。它是一种常见的儿科疾病,发病率呈上升趋势。胰岛移植可能是一种治疗选择,然而,该手术目前的局限性意味着对于大多数1型糖尿病患者来说,尚无治愈方法。转录因子NF-κB因其在1型糖尿病发展中的作用而受到广泛研究。最近的数据表明,NF-κB是自身反应性T细胞激活所必需的,其在单核细胞和树突状细胞中的过度活跃导致细胞因子分泌和抗原呈递改变,最终促成1型糖尿病的发病。NF-κB还被多种促炎细胞因子激活,以调节β细胞的存活和死亡。NF-κB在1型糖尿病中的关键作用使其成为干预该疾病的一个有前景的药物靶点,进一步了解NF-κB信号通路将对新型安全治疗策略的开发具有重要意义。