AIM2 mediates inflammation-associated renal damage in hepatitis B virus-associated glomerulonephritis by regulating caspase-1, IL-1β, and IL-18.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
AIM2 elevation during HBV infection or replication may contribute to inflammatory damage, thus providing a putative therapeutic target for HBV-GN.
School of Medicine, Shandong University, Jinan 250012, China ; Department of Pathology, School of Medicine, Shandong University, Jinan 250012, China.
Junhui
J
Zhen
School of Medicine, Shandong University, Jinan 250012, China ; Department of Liver Disease, Jinan Infectious Disease Hospital, School of Medicine, Shandong University, Jinan 250021, China.
Le
L
Zhang
School of Medicine, Shandong University, Jinan 250012, China ; Department of Liver Disease, Jinan Infectious Disease Hospital, School of Medicine, Shandong University, Jinan 250021, China.
Jiachao
J
Pan
School of Medicine, Shandong University, Jinan 250012, China ; Department of Liver Disease, Jinan Infectious Disease Hospital, School of Medicine, Shandong University, Jinan 250021, China.
Shumin
S
Ma
School of Medicine, Shandong University, Jinan 250012, China.
Xiaojian
X
Yu
Department of Pathology, Harbin Medical University, Harbin 150086, China.
Xiaobo
X
Li
School of Medicine, Shandong University, Jinan 250012, China ; Department of Liver Disease, Jinan Infectious Disease Hospital, School of Medicine, Shandong University, Jinan 250021, China.
Shijun
S
Chen
School of Medicine, Shandong University, Jinan 250012, China ; Digestive Department, Shandong Provincial Qianfoshan Hospital, Shandong University, Jingshi Road No. 16766, Jinan 250014, China.
Wenjun
W
Du
D001706:Biopsy; D020170:Caspase 1 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005921:Glomerulonephritis / Q000150:complications / Q000378:metabolism*; D006509:Hepatitis B / Q000150:complications / Q000378:metabolism*; D006515:Hepatitis B virus; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D020382:Interleukin-18 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D050527:Mesangial Cells / Q000166:cytology; D034741:RNA, Small Interfering / Q000378:metabolism; D012189:Retrospective Studies
C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D020170:Caspase 1