Figure 5.

Phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in human livers chronically infected with hepatitis B virus (HBV). (A, B) Immunohistochemical analysis for pSTAT3 and its subcellular localization in paraffin-embedded liver tissue sections of chronically HBV-infected patients and control individuals. (A) Scale bar: 150 mm. (B) Enlargement, scale bar: 50 mm. The upper row shows nuclear localization of pSTAT3 in hepatocytes, evenly distributed throughout large areas of the liver as it was detected in most sections. The lower row shows alternative, more focal distribution of pSTAT3-positive hepatocytes, very often nearby periportal inflammatory sites. A periportal inflammatory lesion is marked by a dashed line. Arrowheads depict pSTAT3-positive hepatocytes. In some cases, pSTAT3 and its nuclear localization were detected in hepatocytes (arrowhead) and at the same time in sinusoidal macrophages (arrows, middle panels). Occasionally, pSTAT3 was predominantly detected in endothelial cells (arrowhead) and NPCs, most likely Kupffer cells (lower row, right panel). Control livers lack STAT3 phosphorylation and nuclear translocation in hepatocytes or nonparenchymal liver cells (NPCs) in all liver sections investigated. (C) Quantification of pSTAT3-positive cells relative to total number of hepatocytes or NPCs is shown in percent. Black bars represent hepatocytes, green bars represent nonparenchymal liver cells. (D) Western blot analysis of total proteins prepared from healthy liver tissue, from chronically HBV-infected patients or from patients with HBV-related HCC for the presence of pSTAT3. Membranes were reprobed with anti-STAT3 antibodies to control STAT3 expression levels and protein loading.