Zhen Junhui, Zhang Le, Pan Jiachao, Ma Shumin, Yu Xiaojian, Li Xiaobo, Chen Shijun, Du Wenjun
School of Medicine, Shandong University, Jinan 250012, China ; Department of Pathology, School of Medicine, Shandong University, Jinan 250012, China.
School of Medicine, Shandong University, Jinan 250012, China ; Department of Liver Disease, Jinan Infectious Disease Hospital, School of Medicine, Shandong University, Jinan 250021, China.
Mediators Inflamm. 2014;2014:190860. doi: 10.1155/2014/190860. Epub 2014 Feb 20.
BACKGROUND & AIMS: AIM2 plays an important role in innate immunity, but its role in regulating the immune response to hepatitis B virus (HBV) is unknown. We hypothesized that AIM2 expression is positively correlated with HBV-mediated inflammation in patients with HBV-associated glomerulonephritis (HBV-GN), potentiating inflammation and leading to renal damage. We therefore analyzed the expression of AIM2 and inflammatory factors in HBV-GN tissues and cell lines relative to the inflammatory response to HBV infection and HBV status.
Seventy-nine patients with chronic nephritis (CN) were included: 54 with HBV-GN and 24 with chronic glomerulonephritis (CGN). Expression of AIM2, caspase-1, and IL-1β was detected by immunohistochemistry in renal biopsies from each patient. Following siRNA-mediated knockdown of AIM2 in HBV-infected and HBV-uninfected human glomerular mesangial (HGM) cells, expression of caspase-1, IL-1β, and IL-18 was detected by qRT-PCR and Western blot.
AIM2 expression in HBV-GN biopsies (81.4%) was significantly higher than in CGN (4.0%) and positively correlated with caspase-1 and IL-1β expression in HBV-GN. In vitro, AIM2 knockdown reduced caspase-1, IL-1β, and IL-18 expression in HBV-infected and HBV-uninfected HGM cells.
AIM2 elevation during HBV infection or replication may contribute to inflammatory damage, thus providing a putative therapeutic target for HBV-GN.
AIM2在固有免疫中发挥重要作用，但其在调节对乙型肝炎病毒（HBV）免疫反应中的作用尚不清楚。我们假设，在HBV相关性肾小球肾炎（HBV-GN）患者中，AIM2表达与HBV介导的炎症呈正相关，增强炎症并导致肾脏损伤。因此，我们分析了HBV-GN组织和细胞系中AIM2及炎症因子的表达，及其与HBV感染炎症反应和HBV状态的关系。
纳入79例慢性肾炎（CN）患者，其中54例为HBV-GN，24例为慢性肾小球肾炎（CGN）。通过免疫组化检测每位患者肾活检组织中AIM2、半胱天冬酶-1和白细胞介素-1β的表达。在HBV感染和未感染的人肾小球系膜（HGM）细胞中，采用小干扰RNA（siRNA）介导敲低AIM2后，通过实时定量逆转录-聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测半胱天冬酶-1、白细胞介素-1β和白细胞介素-18的表达。
HBV-GN活检组织中AIM2表达（81.4%）显著高于CGN（4.0%），且与HBV-GN中半胱天冬酶-1和白细胞介素-1β表达呈正相关。在体外，敲低AIM2可降低HBV感染和未感染的HGM细胞中半胱天冬酶-1、白细胞介素-1β和白细胞介素-18的表达。
HBV感染或复制过程中AIM2升高可能导致炎症损伤，从而为HBV-GN提供了一个潜在的治疗靶点。
