title: Complement C5 controls liver lipid profile, promotes liver homeostasis and inflammation in C57BL/6 genetic background.
abstract: Innate immunity contributes effectively to the development of alcoholic liver disease (ALD). In special, the activation of the complement system is involved in the pathogenesis of this disease. Here we investigated the contribution of complement C5 protein to the establishment and maintenance of ALD. Eight- to ten-week-old B6C5(+) and B6C5(-) male mice were fed with high fat diet (HFD) only or the same diet containing equicaloric supplements of ethanol (HFDE) or maltodextrin (HFDM) for 10 weeks. Serum parameters of liver function as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), albumin, glucose, triglycerides (TG) and cholesterol were evaluated. Liver tissue samples were collected for histopathological analysis, lipid extraction (TG and cholesterol), cytokines (TNF-α, IL-6, IL-1β, IL-10, IL-12, IL-17, IFN-γ, TGF-β) measurement and NO production. We observed that B6C5(-) mice HFDE-fed accumulated more liver cholesterol and TG, increased liver IL-17 and IL-10 levels and reduced liver TGF-β levels when compared to HFD-fed mice. We also observed that serum AST, AP and albumin were increased in B6C5(-) mice. Liver IL-1β, IL-6, IL-12 and IFN-γ were decreased in B6C5(-) mice independently of diet. We conclude that C5 acts in the control of serum TG and cholesterol, liver cholesterol deposition, liver homeostasis and C5 promotes a pro-inflammatory liver environment in our mouse model of ALD.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Lorena
authors.initials: L
authors.lastname: Bavia
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Íris Arantes
authors.initials: ÍA
authors.lastname: de Castro
authors.affiliation: Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cogliati
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Juliano Bertollo
authors.initials: JB
authors.lastname: Dettoni
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Venancio Avancini Ferreira
authors.initials: VA
authors.lastname: Alves
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil. Electronic address: louisaac@icb.usp.br.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D000431:Ethanol; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000502:physiology*; D008108:Liver Diseases, Alcoholic / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism
chemical_list: D003182:Complement C5; D016207:Cytokines; D014280:Triglycerides; D000431:Ethanol; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase
keywords: Alcoholic liver disease; Cholesterol; Complement C5; Cytokine; Inflammation; Lipid metabolism