cytochalasin-b and Hepatitis-C

It was reported from this laboratory that Kupffer cells (KCs) were activated in patients infected with HCV. Since dendritic cells, monocytes, and macrophages were activated by stimulation with HCV-related proteins, the specific aim of this study was to investigate the role of HCV-related proteins in activation of KCs, the signal pathway of activation of KCs mediated by Toll-like receptor (TLR) 4, and the influence of HCV infection on function of KCs.. Kupffer cells isolated from non-cancerous surgical specimen were co-cultured with HCV-related proteins (Core, NS3, NS4, and NS5), and production of cytokines (TNF-α, IL-1β, and IL-10) and hydrogen peroxide were assessed. Furthermore, effects of neutralization antibodies against the TLR2, TLR3, or TLR4, and cytochalasin B on the production TNF-α by KCs were investigated.. Kupffer cells produced markedly a proinflammatory cytokine TNF-α by stimulation with all HCV-related proteins studied, and values were as same as production by KCs stimulated with LPS. Importantly, this production in the case of NS3 was significantly blunted by about 60% by neutralization antibodies against the TLR4, but not cytochalasin B. Production of TNF-α by isolated KCs stimulated with LPS was significantly greater in the HCV-infected livers than the HCV/HBV-negative livers.. These results indicated that HCV-related proteins may cause prolonged activation of KCs in the HCV-infected liver, leading to accumulation of inflammatory cytokines that contribute to DNA damage and carcinogenesis. Furthermore, function of KCs was difference between patients infected with and without HCV infection.

Topics: Aged; Antibodies, Neutralizing; Cells, Cultured; Coculture Techniques; Cytochalasin B; Female; Hepacivirus; Hepatitis C; Humans; Hydrogen Peroxide; Interleukin-10; Interleukin-1beta; Kupffer Cells; Lipopolysaccharides; Liver; Male; Middle Aged; Toll-Like Receptors; Tumor Necrosis Factor-alpha; Viral Proteins