title: Hepatic expression of CCL2 in alcoholic liver disease is associated with disease severity and neutrophil infiltrates.
abstract: Serum levels and liver expression of CCL2 are increased in patients with alcoholic hepatitis (AH). In an experimental model of alcoholic liver disease (ALD), CCL2 was implicated in proinflammatory cytokines activation and hepatic lipid metabolism, but its role in human disease is currently unknown. In a large cohort of ALD patients, we analysed plasma levels and liver expression of CCL2 and their association with liver disease severity and histological lesions. We also studied the relationship between -2518 A > G CCL2 and CCR2 190 A/G polymorphisms and severity of ALD. We show that CCL2 plasma levels are increased in ALD patients compared with healthy subjects. AH patients had significantly higher plasma levels and hepatic expression of CCL2 than patients without AH. Plasma levels and hepatic expression of CCL2 were associated with disease severity. CCL2 liver expression was correlated with neutrophil infiltrate and interleukin (IL)-8 expression, but not with steatosis. Moreover, there were more G-allele carriers of -2518 A > G CCL2 polymorphism in severe AH patients than in other ALD patients. Our results demonstrate that CCL2 is increased in ALD, particularly in severe forms, and suggest a role for CCL2 in the pathogenesis of ALD via neutrophil recruitment.
authors.affiliation: Laboratory of Experimental Gastroenterology Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital Department of Pathology, Erasme Hospital. Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Degré
authors.forename: A
authors.initials: A
authors.lastname: Lemmers
authors.forename: T
authors.initials: T
authors.lastname: Gustot
authors.forename: R
authors.initials: R
authors.lastname: Ouziel
authors.forename: E
authors.initials: E
authors.lastname: Trépo
authors.forename: P
authors.initials: P
authors.lastname: Demetter
authors.forename: L
authors.initials: L
authors.lastname: Verset
authors.forename: E
authors.initials: E
authors.lastname: Quertinmont
authors.forename: V
authors.initials: V
authors.lastname: Vercruysse
authors.forename: O
authors.initials: O
authors.lastname: Le Moine
authors.forename: J
authors.initials: J
authors.lastname: Devière
authors.forename: C
authors.initials: C
authors.lastname: Moreno
mesh_terms: D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D015331:Cohort Studies; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006519:Hepatitis, Alcoholic / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8