Expression Of TLR3 And TLR4 On Hepatocytes In Patients With Chronic Hepatitis B And Its Clinical Significance

The pathogenesis of chronic hepatitis B has been the focus and difficulty of research in the field of infectious diseases. Now, Infection mechanisms of the hepatitis B virus (Hepatitis B Virus, HBV) in chronic persistent infection have not been elucidated. To understand the pathogenesis of HBV persistent infection is particularly important and urgent. The chronic infection should be the results of innate immune and the adaptive immunity. It is widely recognized that innate immunity may play a more important role in the persistent HBV infection. Toll-like receptors (TLRs) are a kind of innate immune molecules, mainly located in immune cells, especially non-specific immune cells and the surface of some body cells. They not only activate innate immune response, causing the release of cytokines, having a central role in immune and inflammatory responses, but also provide the necessary signals for acquired immune activation, playing an important role in antiviral function. TLR3 recognizes RNA existing in the viral genome or produced on viral replication, and starts the signal transduction pathways to induce nuclear factorκB (NF-κB) translocation and IFN-βexpression. TLR4 acts as a receptor for lipopolysaccharide (LPS), a cell-wall component of Gram-negative bacteria, promptly induces the production of NF-κB and activator protein 1(AP-1). Liver parenchymal cells and nonparenchymal cells express TLR3 and TLR4, signaling of TLR3 and TLR4 might play an important role in the development of the liver disease.ObjeetiveTo investigate the relationship of TLR3 and TLR4 with chronic hepatitis B (CHB),the role of TLR3 and TLR4 in the pathogenesis of CHB and theirs clinical significance, through testing the expression of TLR3 and TLR4 in human liver tissue biopsy specimens from patients with chronic hepatitis B, and the relationship among TLR34 and serum HBV DNA level, clinical severity degrees and histological grades and stages, serum HBeAg.Methodsl.The expression of TLR3 and TLR4 was studied by SABC immunohistochemistry in human livers tissue specimens from 140 patients with chronic viral hepatitis B (CHB). The results were semi-quantitatively evaluated by a scoring system.2.All liver biopsy were confirmed by hematoxylin+eosin (H-E), argyrophilic reticular fiber staining.3.The expression of TLR3 and TLR4 in liver tissue correlation analysis with the clinical severity degrees, histological grades,histological stages, serum HBeAg,serum HBV DNA level.Results1.The positive staining of TLR3 in the liver tissues of patients with CHB was mainly located in cytoplasm and sometimes in cell nucleolus of hepatocytes, the former predominated,but not on cell membrane. Even in one case while intrahepatic lymphocytes, sinusoidal endothelial cell staining. The positive staining of TLR4 in the liver tissues of patients with CHB was mainly located in cytoplasm and sometimes on cell membrane,but not in cell nucleolus of hepatocytes. The expression of TLR3 was weak than that of TLR4.2.The scores of TLR3 expression in the liver tissues of patients with CHB were not correlated with serum HBeAg,serum HBV DNA loads level, the clinical severity degrees,histological stages,and histological stages (P<0.05)3.There were significant different scores of TLR4 expression in patients with mild, moderate and severe CHB (H=16.59,P<0.05).The scores of TLR4 expression in the liver tissues of patients with CHB were positively correlated with the clinical severity degrees(rs=0.339, P<0.05). The scores of TLR4 expression were linear relationship with the clinical severity degrees (P<0.05), The expression intensity of TLR4 increased gradually along with the increase of clinical severity degree.4.There were significant different scores of TLR4 expression in patients with histological inflammation grades(P<0.05). The scores of TLR4 expression in the liver tissues of patients with CHB were positively correlated with histological inflammation grades (rs=0.574, P<0.05),The scores of TLR4 expression were linear relationship with histological severity (P<0.05), The expression intensity of TLR4 increased gradually along with the increase of histological grades.There were aslo significant differences of TLR4 expression in patients with histological fibrosis (P<0.05).5. The scores of TLR4 expression in the liver tissues of patients with CHB were positively correlated with histological fibrosis stages(rs=0.485, P<0.05), The scores of TLR4 expression have a linear relationship with histological stages (P<0.05), The expression intensity of TLR4 increased gradually along with the liver histological fibrosis..6. The scores of TLR4 expression in the liver tissues of patients with CHB were not correlated with serum HbeAg status or serum HBV DNA loads level (P<0.05)Conclusions1.The expression of TLR4 increased in the liver tissues of patients with CHB, and TLR4 had a correlationship with the grade of necroinnammatory activity of CHB, fibrosis of CHB and clinical severity degrees. The expression of TLR4 had not a correlationship with serum HbeAg status and serum HBV DNA level. TLR4 may play an important role in the pathogenesis of CHB.2. The expression of TLR3 was weak in the liver tissues of CHB patients with different histological stages, and he scores of TLR3 expression in the liver tissues of patients with CHB were not correlated with serum HbeAg status or serum HBV DNA loads. That the expression of TLR3 was not stimulated HBV infection, and we expected that TLR3-induced intracelluar antiviral activity was not also activated, which may one of reasons leading to chronic HBV infection.