Expression Of AIM2Is Correlated With Increased Inflammation In Chronic Hepatitis B Patients

Background and ObjectiveThe exact pathogenesis of Chronic Hepatitis B(CHB)remains unclear. It is generally thought that hepatocyte injury is not caused directly by virus in the cells. But rather in drawing nourishment from the cytoplasm, the virus exists and develops cccDNA, then damage frequently occur. Such reproduction provides huge amounts of HBeAg and HBsAg, fixing a position on the cell membrane, continually arousing the immune system to recognize them, suffering liver damage.AIM2means absent in melanoma2, as a kind of Tumor-inhibiting Factor, it was thought to act as a tumor suppressor by repressing NF-κB transcriptional activity and inhibit the growth of carcinoma. AIM2may also be able to be an oncogene in some types of cancer. Recent research has demonstrated that AIM2plays an important role in innate immune response through sensing potentially dangerous cytoplasmic DNA and inducing the formation of the ASC pyroptosome. ASC is part of the inflammasome, can sensing extracellular signal and activating caspase-1, the CARD domain in the caspase-1can bind homotypic domain joint in the inflammasome[1The AIM2is reported to be constitutively expressed in the spleen, small intestine and orchis. It seems like that the expression of human AIM2is IFN-inducible and is related to immunological reaction. It belongs to a family of IFN-inducible proteins that is the HIN-200family, We grouped many proteins in this family because all proteins contain two specific motifs:the pyrin domain (PYD)and the oligonucleotide/oligosaccharide-binding domain(OB-folds). The OB-folds are found in other proteins that can bind double-strand DNA. The PYD domain, is known to bind ASC (apoptotic speck protein containing a CARD). Then ASC dimerized and forms inflammasomes, we hypothesized the level of AIM2are corresponding with HBV infection. Then activates inflammatory mechanisms and causes hepatic injury.ASC is a kind of proteins that is composed of two do-mains, the caspase protein-containing domain (CARD) and PYD. PYD and CARD is homologous protein-protein interaction domains, and plays a very important role in the oligomerization of ASC[2-3], and mediates Pyroptosis-like cell death. Caspase-1belongs to the cysteine-aspartic acid protease (caspase) family. Can also be referred to as IL-1β-converting enzyme. Previous studies determined the region is located in11q22-q23. Caspase exist as an inactive phase, When the cells affected by various extracellular pathogens or stimulated by intracellular dangerous signals, it will undergoing proteolytic processing, producing2subunits, p20and p10, that dimerized to p20/p10-dimer, then p20/p10-containing heterotetramer, the active form eventually becomes.Therefore, to explore the role of AIM2associated with Chronic Hepatitis B and to get some insight into whether AIM2induces caspase-1activation, processing the inactivate pro-interleukin-IL1β (pro-IL1(3)and pro--interleukin-IL18(pro-IL18) to their active state.MethodsThe sample are chosen by way of liver puncture (CHB,china’s main nationality,n=70), and divided into two groups, the experimental group is mild and moderate to serious hepatitis B, those fatty liver disease are in contrast group. Using the immunohistochemistry to detect AIM2、Caspase-1、IL-18、L-1β expression in liver tissues of experimental and contrast groups. Comparison between the groups were by chi-square test.and the correlation analysis used spearman test.ResultsThe positive rate of AIM2expression was89.3%in experimental group was significantly higher than that43.5%in control group (x2=15.655, P＜0.01).In experimental Group, the level of caspase-1has positive correlation with the level of AIM2(rs=0.738, p＜0.01), the level of IL-1β has positive correlation with level of caspase-1(rs=0.447, p＜0.01), the level of IL-18has positive correlation with level of caspase-1(rs=0.513,p＜0.01). The level of ALT and AST has positive correlation with the level of AIM2,(rs=0.325,0.362,p＜0.01). The level of AIM2in high replication group(HBV-DNA≥1*10^5copies/ml) was significantly higher than that in low replication group (HBV-DNA＜1*10^5copies/ml)(x2=27.572,P＜0.01). And the level of AIM2in experimental Group were significantly higher than those whose are in contrast group.ConclusionsDuring innate immune response to hepatitis B infection, AIM2may sense HBV-DNA resulting in liver immune injury though activing Caspase-1and further inducing release IL-1β, IL-18inflammatory factors.