Hepatic steatosis causes induction of the chemokine RANTES in the absence of significant hepatic inflammation.

Abstract	Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to cirrhosis. Hepatocellular lipid accumulation is a hallmark of both nonalcoholic steatosis and steatohepatitis (NASH). The latter develops upon pro-inflammatory cell infiltration and is widely considered as the first relevant pathophysiological step in NAFLD-progression. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. We here aimed to investigate its expression in NAFLD. Incubation of primary human hepatocytes with palmitic acid induced a dose-dependent lipid accumulation, and corresponding dose-dependent RANTES induction in vitro. Furthermore, we observed significantly elevated hepatic RANTES expression in a dietary model of NAFLD, in which mice were fed a high-fat diet for 12 weeks. This diet induced significant hepatic steatosis but only minimal inflammation. In contrast to the liver, RANTES expression was not induced in visceral adipose tissue of the group fed with high-fat diet. Finally, RANTES serum levels were elevated in patients with ultrasound-diagnosed NAFLD. In conclusion, our data indicate hepatocytes as cellular source of elevated hepatic as well as circulating RANTES levels in response to hepatic steatosis. Noteworthy, upregulation of RANTES in response to lipid accumulation occurs in the absence of relevant inflammation, which further indicates that hepatic steatosis per se has pathophysiological relevance and should not be considered as benign.
Authors	Georgi Kirovski, Erwin Gäbele, Christoph Dorn, Lukas Moleda, Christoph Niessen, Thomas S Weiss, Hella Wobser, Doris Schacherer, Christa Buechler, Hermann E Wasmuth, Claus Hellerbrand
Journal	International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 3 Issue 7 Pg. 675-80 (Aug 02 2010) ISSN: 1936-2625 [Electronic] United States
PMID	20830238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Chemokine CCL5
Topics	Animals Cell Line Chemokine CCL5 (biosynthesis) Fatty Liver (metabolism, pathology) Hepatitis (metabolism, pathology) Humans Male Mice Mice, Inbred BALB C

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