Hepatitis C Virus (HCV)-Induced Inflammation: The Role of Cross-Talk Between HCV-Infected Hepatocytes and Stellate Cells



Fig. 9.1
Cross-talk between hepatitis C virus (HCV)-infected hepatocytes and hepatic stellate cells (HSCs) induces macrophage inflammatory protein (MIP)-1β expression. (a) Hepatocytes or HCV-infected hepatocytes were cultured alone or in the presence of HSCs for 24 h. The expression of MIP-1β was measured by quantitative real-time polymerase chain reaction (qRT-PCR). (b) Hepatocytes or HCV-infected hepatocytes were treated with conditioned medium from hepatocytes (Hepatocyte-CM) or HSCs (HSC-CM) for 24 h. The expression of MIP-1β was measured by qRT-PCR. (c) HSCs were treated with transforming growth factor (TGF)-β1 for 24 h. Hepatocytes or HCV-infected hepatocytes were treated with HSC-CM or TGF-β1-stimulated HCS-CM for 24 h. The expression of MIP-1β was measured by qRT-PCR



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Fig. 9.2
Interleukin (IL)-1α and CCAAT (cytosine–cytosine–adenosine–adenosine–thymidine)-enhancer-binding protein (C/EBP)-β contribute to the hepatitis C virus (HCV)-infected hepatocyte response to hepatic stellate cells (HSCs). (a) HCV-infected hepatocytes were cultured with HSCs together with an isotype control, anti-IL-1, or IL-1 receptor antagonist (IL-1RA) for 24 h. Macrophage inflammatory protein (MIP)-1 expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). (b) Hepatocytes or HCV-infected hepatocytes were treated with various amounts of recombinant IL-1 (0, 0.1, 1.0, 10, or 100 pg/ml) for 24 h. MIP-1 expression was analyzed by qRT-PCR. (c) Hepatocytes and HCV-infected hepatocytes were transfected with control small-interfering RNA (siRNA) or small-interfering C/EBP (siC/EBP)-β. After 24 h of transfection, the cells were treated with conditioned medium from hepatocytes (Hepatocyte-CM) or HSCs (HSC-CM) for 24 h. MIP-1 expression was analyzed by qRT-PCR


These results suggest that TGF-β, which is induced by HCV infection, stimulates quiescent HSCs, and activation or trans-differentiation of HSCs leads to the expression of IL-1α, resulting in increased levels of inflammatory cytokines and chemokines in HCV-infected hepatocytes (Fig. 9.3).

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Fig. 9.3
Cross-talk between hepatitis C virus (HCV)-infected hepatocytes and hepatic stellate cells (HSCs). (a) HCV infection induces the expression of growth factors, such as transforming growth factor (TGF)-β. (b) When quiescent HSCs are activated by growth factors, activated HSCs secrete inflammatory cytokines, such as interleukin (IL)-1α. (c) HCV-infected cells are stimulated by IL-1α. An increase in inflammatory cytokine production accelerates inflammation in the liver



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Dec 10, 2016 | Posted by in ONCOLOGY | Comments Off on Hepatitis C Virus (HCV)-Induced Inflammation: The Role of Cross-Talk Between HCV-Infected Hepatocytes and Stellate Cells

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