Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH

• DOI: 10.1002/hep.26749
• Publication Date: 2013-10-12T01:48:04Z
• Authors: Salvatore Sutti; Aastha Jindal; Irene Locatelli; Marco Vacchiano; Luca Gigliotti; Cristina Bozzola; Emanuele Albano
• Keywords: CD4-Positive T-Lymphocytes; Male; 0303 health sciences; Adaptive Immunity; 3. Good health; Fatty Liver; Killer Cells, Natural; Mice, Inbred C57BL; Disease Models, Animal; Mice; Oxidative Stress; 03 medical and health sciences; Liver; Non-alcoholic Fatty Liver Disease; Disease Progression; Animals; Humans; Lipid Peroxidation

Previous studies have shown that human nonalcoholic steatohepatitis (NASH) is often associated with the presence of circulating antibodies against protein adducted by lipid peroxidation products. Here we used methionine-choline deficient (MCD) model NASH to characterize possible involvement adaptive immunity in NASH. In mice fed up 8 weeks MCD diet extension liver injury and lobular inflammation paralleled development immunoglobulin G (IgG) malonyldialdehyde (MDA) 4-hydroxynonenal (4-HNE)-derived antigens as well hepatic recruitment CD4(+) CD8(+) T-lymphocytes responsive same antigens. Moreover, these animals individual IgG reactivity MDA-adducts positively correlated transaminase release tumor necrosis factor alpha (TNF-α) expression. To substantiate role immune responses triggered oxidative stress progression NASH, were immunized MDA-adducted bovine serum albumin (MDA-BSA) before feeding diet. MDA-BSA immunization did not affect control livers, but further stimulated release, inflammation, expression proinflammatory cytokine MCD-fed mice. The increased severity involved T helper (Th)-1 activation cells that, turn, macrophage M1 responses. fibrosis was also evident relation an IL-15-mediated increase natural killer T-cells (NKT) up-regulation production osteopontin NKT macrophages. These results indicate can contribute stimulating both humoral cellular responses, pointing pathogenesis disease.