黑色素瘤缺乏因子2在炎症、免疫和肿瘤发生发展中的作用  

Role of Absent in Melanoma 2 in Development of Inflammation,Immunity and Cancer

作　　者：刘伊偲 胡容 LIU Yi-si;HU Rong(School of Basic Medical and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学基础医学与临床药学学院,江苏南京210009

出　　处：《药物生物技术》2018年第4期354-358,共5页Pharmaceutical Biotechnology

基　　金：国家自然科学基金面上项目(No.81672816)

摘　　要：黑色素瘤缺乏因子2(Absent in melanoma 2,AIM2)是固有免疫系统中的一种感受器分子,它能够特异性地识别细胞质当中变异或异位的DNA分子,包括受损的DNA分子以及由于细胞核核膜破裂而泄露在胞浆当中的DNA片段。同时,AIM2还是一个重要的病原体感受器,它能在细胞受到病毒、细菌及寄生虫等侵扰时监测外源性DNA在胞浆当中的积累情况。AIM2的激活会启动炎症小体的装配,这种固有免疫复合物可以激活炎性半胱天冬酶(Caspase)通路,并促使细胞因子白介素-1β(IL-1β)及白介素-18(IL-18)的成熟与分泌,最终导致细胞凋亡的发生。AIM2炎症小体还参与多种生理过程,并与许多疾病的发生发展有关,如自发性炎症疾病与自体免疫性疾病。近期研究表明,AIM2对肿瘤的发生发展过程也产生重要影响,AIM2对肿瘤的调控与肿瘤的种类有关,其作用机制也不尽相同。AIM2可以影响多种信号通路,包括细胞增殖、细胞周期和侵袭转移,以及通过维持菌群内稳态环境从而影响肿瘤的发展。因此,除了作为病原体相关分子模式(Pathogen associated molecular patterns,PAMPs)的感受器,AIM2炎症小体还能影响多种疾病的发生与发展。文章总结了AIM2对不同疾病的影响,并分别讨论了其作用机制。Absent in melanoma 2（ AIM2） was a kind of DNA sensor in the innate immune system,which could specifically recognize the DNA molecule of altered form or mislocalized DNA molecule in cytoplasm,including damaged DNA molecule and DNA fragments released from nuclear due to the loss of nuclear integrity. In the meanwhile,AIM2 played a role in sensing pathogens as an important sensor of pathogens,which could detect the accumulation of exogenous DNA in the cytoplasm because of the invasion and infection of viruses,parasites and bacteria. The activation of AIM2 triggered inflammatory corpuscle assembly. This complex of innate immune system then activated the inflammatory caspase signaling pathways,promotes the maturation and secretion of interleukin-1 a（ IL-1 a） and interleukin-18（ IL-18）,at last led to the initiation of pyroptosis process. Besides the role of inflammasome,AIM2 engaged in multiple physiology events,and contributed to the development of several diseases,such as autoinflammation and autoimmune diseases. Moreover,recent researches demonstrated that AIM2 also exerted important role on the occurrence of tumor development both in clinical studies and in-vitro experiments. However,the effects of AIM2 on cancer are complicated. The expression of AIM2 could inhibit or promote the development of cancer depending on the specific kinds of cancer,and its underlying mechanisms varied with the types as well. From the researches published,AIM2 could interact with several signaling pathways in cancer cells,including proliferation,cell cycle,invasion and metastasis,and pyrotosis. In addition,AIM2 could regulate the development of cancer by maintaining flora homeostasis environment. To sum up,AIM2 could not only function as the sensor of pathogens associated molecular patterns（ PAMP）,but also exert influence on the development of various diseases,such as inflammation,autoimmunity diseases and cancer. The different functions of AIM2 in several diseases were reviewed and the diversified mechanisms of AIM2 were

关 键 词：黑色素瘤缺乏因子2 炎症小体 炎症 自体免疫性疾病 肿瘤 半胱天冬酶 

分 类 号：Q51[生物学—生物化学] R73[医药卫生—肿瘤]