Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

Abstract

Toll-Like Receptors and Nuclear Factor Kappa-B as a Cross-Bridge between Inflammation and Carcinogenesis in Chronic Viral Hepatitis

Author(s): Nadia A Hussein, Hamda H El-Sayed, Ola M Mahmoud, Mona M Nosseir, Omar M Sabry, Mohey E Attia, Faiza M Essawy

Toll-like Receptors (TLRs) are not only crucial for the initiation of immune response, but also play a key role in several inflammatory diseases. This study postulated a potential contribution of TLR3 and TLR9 in the initial triggering of inflammatory ambiance via Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) activation in Chronic Virus Hepatitis (CVH) with later participation in inflammation induced carcinogenesis. The study was carried out on a 100 of chronic hepatitis Egyptian patients: 50 of virus C (CHC) and 50 of virus B (CHB) etiologies including: 20 and 15 cases with mild liver fibrosis (stages 1 or 2), 10 and 15 cases with liver cirrhosis (stage 4) and 40 cases of virus associated Hepatocellular Carcinoma (HCC), 20 of each etiology, respectively. Fifteen gender and age-matched, individuals were enrolled in the study as healthy controls. Toll-like receptor 3 or 9 expression on peripheral blood monocytes and liver tissue was evaluated in CHC and CHB patients respectively and in control cases. Liver tissue NF-κB expression and serum levels of Tumor Necrosis Factor-α (TNF-α), Interleukin (IL)-1β and IL-6 were measured in all cases of the study. The results showed a significant increase of all parameters in CHC and CHB patients compared to controls. Gradual but significant increment was recorded from mild fibrosis to cirrhosis, reaching the highest in HCC groups. Increased expression of TLRs in peripheral blood monocytes and liver tissue was running hand in hand with increased serum levels of TNF-α, IL- and IL-6 favoring the current postulation. This was further supported by the parallel increase in NF-κB expression in liver tissue especially in HCC group suggesting a potential link between chronic hepatic injury, fibrosis and HCC. These findings await further implementation and inclusion in therapeutic research.


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