Lack of CC chemokine ligand 2 differentially affects inflammation and fibrosis according to the genetic background in a murine model of steatohepatitis
| Autor: | Irene Locatelli, Francesco Vizzutti, N. Navari, Emanuele Albano, Alessandra Caligiuri, Erica Novo, Maurizio Parola, Massimo Pinzani, W. Delogu, E. Zamara, Fabio Marra, Salvatore Sutti, S. Galastri, E. Vivoli, A. Provenzano, Stefano Milani |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Liver Cirrhosis
HNE 4-hydroxynonenal IFN-γ interferon-γ Adipose tissue AST aspartate aminotransferase iNOS inducible NO synthase chemistry.chemical_compound Mice 0302 clinical medicine CC chemokine ligand 2 Fibrosis Transforming Growth Factor beta cytokine Chemokine CCL2 liver fibrosis Mice Knockout 0303 health sciences TIMP-1 tissue inhibitor of metalloproteinases-1 Mice Inbred BALB C Fatty liver CCL2 CC chemokine ligand 2 General Medicine MGL1 macrophage galactose-type C-type lectin 1 GAPDH glyceraldehyde-3-phosphate dehydrogenase TNFα tumour necrosis factor α 030211 gastroenterology & hepatology non-alcoholic steatohepatitis Research Article medicine.medical_specialty NAFLD non-alcoholic fatty liver disease ALT alanine transaminase NASH non-alcoholic steatohepatitis Biology S2 Collagen Type I 03 medical and health sciences ROS reactive oxygen species Species Specificity Internal medicine TGF-β transforming growth factor-β medicine Hepatic Stellate Cells Animals Sirius Red 030304 developmental biology KO knockout Tissue Inhibitor of Metalloproteinase-1 Macrophages chemokine medicine.disease WT wild-type Dietary Fats IL interleukin Fatty Liver Mice Inbred C57BL Disease Models Animal Oxidative Stress Endocrinology chemistry Alanine transaminase Immunology CCR2 CC chemokine receptor 2 Hepatic stellate cell biology.protein Steatosis Steatohepatitis RT real-time FAM 6-carboxyfluorescein MCD diet methionine/choline-deficient diet |
| Zdroj: | Clinical Science (London, England : 1979) Clinical Science Clinical Science; Vol 123 |
| ISSN: | 1470-8736 0143-5221 |
| Popis: | Expression of CCL2 (CC chemokine ligand 2) (or monocyte chemoattractant protein-1) regulates inflammatory cell infiltration in the liver and adipose tissue, favouring steatosis. However, its role in the pathogenesis of steatohepatitis is still uncertain. In the present study, we investigated the development of non-alcoholic steatohepatitis induced by an MCD diet (methionine/choline-deficient diet) in mice lacking the CCL2 gene on two different genetic backgrounds, namely Balb/C and C57/Bl6J. WT (wild-type) and CCL2-KO (knockout) mice were fed on a lipid-enriched MCD diet or a control diet for 8 weeks. In Balb/C mice fed on the MCD diet, a lack of CCL2 was associated with lower ALT (alanine transaminase) levels and reduced infiltration of inflammatory cells, together with a lower generation of oxidative-stress-related products. Sirius Red staining demonstrated pericellular fibrosis in zone 3, and image analysis showed a significantly lower matrix accumulation in CCL2-KO mice. This was associated with reduced hepatic expression of TGF-β (transforming growth factor-β), type I procollagen, TIMP-1 (tissue inhibitor of metalloproteinases-1) and α-smooth muscle actin. In contrast, in mice on a C57Bl/6 background, neither ALT levels nor inflammation or fibrosis were significantly different comparing WT and CCL2-KO animals fed on an MCD diet. In agreement, genes related to fibrogenesis were expressed to comparable levels in the two groups of animals. Comparison of the expression of several genes involved in inflammation and repair demonstrated that IL (interleukin)-4 and the M2 marker MGL-1 (macrophage galactose-type C-type lectin 1) were differentially expressed in Balb/C and C57Bl/6 mice. No significant differences in the degree of steatosis were observed in all groups of mice fed on the MCD diet. We conclude that, in experimental murine steatohepatitis, the effects of CCL2 deficiency are markedly dependent on the genetic background. |
| Databáze: | OpenAIRE |
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