Study of toll-like receptor 7 expression and interferon α in Egyptian patients with chronic hepatitis C Infection and Hepatocellular Carcinoma

Abstract

Background: Hepatitis C virus is considered to be one of the most important devastating causes of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. Toll-like receptor 7 (TLR7) is a pathogen-recognition receptor that is expressed on innate immune cells. It recognizes viral RNA which induces its activation with a subsequent increase in IFN-a transcription. It has been postulated that HCV may cause down regulation of these receptors as one of immune evading mechanisms that participate in viral persistence.The aim of the work: Was to investigate the expression of TLR7 in peripheral blood of patients with chronic HCV infections and patients with HCC, comparing it with normal individuals, and correlating it with both serum levels of IFN-a and viral load.Results: The results of this study showed a significant decrease in TLR7 expression in patients with chronic HCV and no detection at all in patients with HCC, in addition a significant negative correlation was observed between levels of TLR7expression and interferon a when compared to viral load.Conclusion: Down regulation of TLR7 expression in HCV and HCC patients may contribute to the decrease of IFN-a and increase in viral load. These results raise the possibility that by targeting TLR7 with high affinity pharmacological stimulants may be able to control HCV infection by induction of IFN-a and direct activation of antiviral mechanisms in hepatocytes. Additionally, they provide insight about the potential use of TLR7 as a new set of molecular markers for prognosis and outcomes of chronic HCV infection and HCC.Ó 2014 Production and hosting by Elsevier B.V. on behalf of Ain Shams University.

Relative Expression of Toll-Like Receptors 2 and 7 mRNA in Peripheral Blood of Patients With Hepatitis C

“…Also, Sato et al reported that the expression level of TLR4, TLR7 and TLR8 in CD14 + monocytes of Peripheral Blood Mononuclear Cells (PBMCs), from HCV-infected patients, significantly increased compared to those of controls, while the expression levels of the other TLRs were similar between the patients and the controls ( 20 ). In contradiction to these results, Abdel-Raouf et al showed that there was a highly significant decrease in TLR7 mRNA expression in PBMCs of HCV-infected subjects compared to the control group and in hepatocellular carcinoma group ( 21 ). These findings of Abdel-Raouf et al were in agreement with the results of Atencia et al, which found a significant down regulation in TLR3 and TLR7 mRNA levels in chronic HCV infection with cirrhosis compared to healthy controls ( 14 ).…”

TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway

“…To explore the potential mechanisms by which Imiquimod suppresses CSC numbers, it was hypothesized that Imiquimod inhibited malignant cellular behaviors in HCC cells and HCC stem cells through downregulation of IKK-NFκB-IL6 signaling, which had previously been demonstrated to function in TLR7-dominated hepatic diseases ( 8 , 9 , 19 ). The expression levels of IKK, NFκB and IL6 were all significantly decreased in the Imiquimod-treated group (P<0.01; Fig.…”

Viruses Seen by Our Cells: The Role of Viral RNA Sensors

“…Moreover, the potential capacity of the vRNA of different influenza strains to stimulate TLRs 7 and 8 was found to be correlated to the virulence of the strains [ 141 ]. In addition, SNPs in the TLR7 and TLR8 genes were associated with the CD4 T cell count during an HIV infection [ 142 ] as well as the levels of type 1 IFN and proinflammatory cytokines and the progression to hepatocellular carcinoma during an HCV infection [ 143 , 144 ]. Also, the low copy numbers of the TLR7 gene is associated with the establishment of chronic HBV infection [ 145 ].…”