title: Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.
abstract: Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: McMahan
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Cara E
authors.initials: CE
authors.lastname: Porsche
authors.affiliation: Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Edwards
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, Colorado, United States of America.|Department of Microbiology and Immunology, University of Colorado Denver, Aurora, Colorado, United States of America.|Denver Veteran's Affairs Medical Center, Denver, Colorado, United States of America.
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Rosen