Hepatitis C Virus (HCV)-induced inflammation: The role of cross-talk between HCV-infected hepatocytes and stellate cells

Hepatitis C virus (HCV) is a major public health problem, as 170 million people worldwide are currently chronically infected with the virus. HCV infection leads to chronic inflammation, which is the initial step toward fibrosis and is a significant risk factor for developing hepatocellular carcinoma. HCV-induced liver inflammation involves several events, such as modification of cytokine and chemokine pathways, oxidative stress, and induction of steatosis. Recent studies have revealed that not only HCV-infected hepatocytes but also neighboring cells, such as lymphocytes, Kupffer cells and hepatic stellate cells (HSCs), play important roles in HCV-induced inflammation. In the current study, we found evidence of cross-talk between HCV-infected hepatocytes and HSCs, revealed by the production of cytokines and chemokines. Upon co-culture of HSCs with HCV-infected hepatocytes in vitro, HSCs stimulated HCV-infected hepatocytes to produce pro-inflamatory cytokines and chemokines, including interleukin (IL)-6, IL-8, macrophage inflammatory protein (MIP)-1α and MIP-1β. This cross-talk is likely to be a key feature of inflammatory diseases caused by HCV infection.