RESEARCH ARTICLE In Vivo Zonal Variation and Liver Cell-Type Specific NF-κB Localization after Chronic Adaptation to Ethanol and following Partial

NF-κB is a major inflammatory response mediator in the liver, playing a key role in the path-ogenesis of alcoholic liver injury. We investigated zonal as well as liver cell type-specific dis-tribution of NF-κB activation across the liver acinus following adaptation to chronic ethanol intake and 70 % partial hepatectomy (PHx). We employed immunofluorescence staining, digital image analysis and statistical distributional analysis to quantify subcellular localiza-tion of NF-κB in hepatocytes and hepatic stellate cells (HSCs). We detected significant spa-tial heterogeneity of NF-κB expression and cellular localization between cytoplasm and nucleus across liver tissue. Our main aims involved investigating the zonal bias in NF-κB localization and determining to what extent chronic ethanol intake affects this zonal bias with in hepatocytes at baseline and post-PHx. Hepatocytes in the periportal area showed higher NF-κB expression than in the pericentral region in the carbohydrate-fed controls, but not in the ethanol group. However, the distribution of NF-κB nuclear localization in hepato-cytes was shifted towards higher levels in pericentral region than in periportal area, across all treatment conditions. Chronic ethanol intake shifted the NF-κB distribution toward