The significance of Toll-like receptor 4 (TLR4) expression in patients with chronic hepatitis B

Abstract

Results: TLR4 expressed mainly in the cytoplasm and some on cell membrane in hepatocytes. The staining scores of TLR4 expression in the liver tissues of patients with CHB were significantly higher than that of healthy controls. The liver tissues from patients with severe CHB expressed higher level of TLR4 than those from patients with mild CHB. Furthermore, the staining scores of TLR4 expression in the liver tissues of patients with CHB were positively correlated with the grading scores. Our results also showed that the mean fluorescence intensity and TNFsecretion induced by endotoxin as well as the protein and mRNA 1eve1s of TLR4 in HepG2.2.15 cells were all significantly higher than those in HepG2 cells. Conclusion: TLR4 was up-regulated in the hepatocytes in patients with CHB. This indicates a potentially important interaction between TLR4 expression and the pathogenesis of CHB.Mechanisms responsible for chronic hepatitis B remain incompletely understood, although increasing evidence points to immunological rather than direct viral effects playing a central role. 1,2 However, most studies have focused on adaptive immunity, with little research on the innate immunity. One of the key components of the innate immune response is the family of Toll-like receptors(TLRs), evolutionarily conserved pattern recognition receptors. Activation of TLRs triggered by various motifs common to microorganisms, known as pathogen-associated molecular patterns, can promote the inflammatory response, the antiinfectious response and the maturation of antigen pre-ORIGINAL RESEARCH

Single-nucleotide polymorphism of Toll-like receptor 4 and interleukin-10 in response to interferon-based therapy in Egyptian chronic hepatitis C patients

“…This increase is in agreement with the results of He et al [44] and Wei et al [45], who reported that TLR mRNA levels were increased significantly in chronic HCV and HBV patients.…”

The Incidence and Significance of Pattern-Recognition Receptors in Chronic Viral Hepatitis Types B and C in Man

“…Its expression was found to be higher in the hepatocytes of patients with hepatitis B than in those of healthy controls. Moreover, the intensity of the immunohistochemical reaction positively correlated with grading scores (Wei et al 2008). We were able to demonstrate TLR4, TLR2, and TLR3 staining of hepatocytes in the livers of children with hepatitis C. The reaction was both cytoplasmic and cell membrane bound, but the former predominated (Mozer- Lisewska et al 2005).…”

Pattern recognition receptor responses in children with chronic hepatitis B virus infection

“…12,27 Opposing results have demonstrated that cell surface expression of TLR2 on PBMCs was significantly reduced in patients with CHB compared to healthy controls, and when stimulated with TLR2 and TLR4 agonists, PBMCs from patients with CHB exhibited decreased ability to produce cytokines (IL-6, IL-8, IL-12 and TNF-␣) compared with those from healthy controls. 9 Another group reported that PBMC expression of TLR2 was significantly reduced in HBeAg-positive patients compared to both controls and HBeAg-negative patients 10 and the same group demonstrated that the expression level of TLR2 was downregulated on PBMCs, hepatocytes and Kupffer cells from patients with HBeAg positive CHB as compared with HBeAg-negative CHB.…”