结肠中信号转导和转录激活因子相互作用分子（SIGIRR）的异位表达通过下调Toll样受体4（TLR4）/核因子κB（NF-κB）的过度激活来改善小鼠结肠炎。
Ectopic expression of SIGIRR in the colon ameliorates colitis in mice by downregulating TLR4/NF-κB overactivation.
作者信息
Liu Jinlin, Chen Yanxia, Liu Dongsheng, Liu Wei, Hu Sijun, Zhou Nanjin, Xie Yong
机构信息
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China; Institute of Molecular Medicine, Jiangxi Academy of Medical Sciences, No. 461, Bayi Road, Nanchang, China; Department of Clinical Laboratory, Zhejiang Provincial People's Hospital,158 Shangtang Road, Hangzhou, China.
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China; Department of Rheumatology, Zhejiang Provincial People's Hospital,158 Shangtang Road, Hangzhou, China.
出版信息
Immunol Lett. 2017 Mar;183:52-61. doi: 10.1016/j.imlet.2017.01.015. Epub 2017 Jan 30.
BACKGROUND
Inflammatory bowel disease (IBD) is characterized by uncontrolled immune responses in inflamed mucosa, especially the TLR (Toll-like receptor) signaling pathway. Single Ig domain containing IL-1 receptor-related molecule (SIGIRR), a negative regulator of the TLR signaling pathway, whether had a therapeutic effect in a mouse model of IBD, and the underlying mechanism has not been investigated.
METHODS
Coacervation was used to prepare chitosan/pUNO-SIGIRR nanoparticles. The nanoparticles were administered to mice with colitis using enteroclysis. The disease activity index (DAI) and hematoxylin and eosin staining (HE) staining were used to evaluate the therapeutic effects of the SIGIRR nanoparticles. Immunohistochemistry was performed to elucidate the underlying mechanism driving these effects.
RESULTS
Chitosan/pUNO-SIGIRR nanoparticles were successfully constructed and were spherical, with a mean diameter of less than 100nm, and the plasmid encapsulating efficiency was 99.9%. The chitosan/pUNO-SIGIRR nanoparticles attenuated colonic tissue inflammation through the inhibition of TLR4/NF-κB overactivation by downregulating TLR4, MyD88 and NF-κB p65 expression in a mouse model of colitis.
CONCLUSIONS
The novel chitosan/pUNO-SIGIRR nanoparticles had a therapeutic effect on IBD in a mouse model through the inhibition of TLR4/NF-κB overactivation.
背景
炎症性肠病（IBD）的特征在于炎症黏膜中不受控制的免疫反应，尤其是Toll样受体（TLR）信号通路。含单个免疫球蛋白结构域的白细胞介素-1受体相关分子（SIGIRR）是TLR信号通路的负调节因子，其在IBD小鼠模型中是否具有治疗作用及其潜在机制尚未得到研究。
方法
采用凝聚法制备壳聚糖/pUNO-SIGIRR纳米粒。通过灌肠将纳米粒给予结肠炎小鼠。使用疾病活动指数（DAI）和苏木精-伊红染色（HE）评估SIGIRR纳米粒的治疗效果。进行免疫组织化学以阐明产生这些效果的潜在机制。
结果
成功构建了壳聚糖/pUNO-SIGIRR纳米粒，其呈球形，平均直径小于100nm，质粒包封率为99.9%。在结肠炎小鼠模型中，壳聚糖/pUNO-SIGIRR纳米粒通过下调TLR4、髓样分化因子88（MyD88）和核因子κB p65的表达，抑制TLR4/核因子κB过度激活，从而减轻结肠组织炎症。
结论
新型壳聚糖/pUNO-SIGIRR纳米粒通过抑制TLR4/核因子κB过度激活，对IBD小鼠模型具有治疗作用。
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