MiR-155 is involved in immune and inflammatory diseases and associated with liver fibrosis and steatohepatitis. However, the mechanisms involved in miR-155 regulation of liver injury are largely unknown. We aimed to unveil the role of mir-155 in acute liver injury.
Acetaminophen (APAP) and Concanavalin A (ConA) models were performed in wild type (WT) and miR-155-/- deficient mice. MiR-155-/- mice were transplanted with WT bone marrow cells. Liver injury, cytokine expression and inflammatory recruitment were assessed.
ConA but not APAP increased the expression of miR-155 in liver tissue. ConA induced an increase of transaminases (AST, ALT and LDH) and expression of pro-inflammatory cytokines (Cxcl1, 5,9, 10, 11, Ccl2, 20 and Icam1) in miR-155-/- mice as compared to wt. Importantly, these animals showed a significant decrease in CD4+CXCR3+ cells recruitment but no changes in total CD4+, CD8+, infiltrating monocytes and NKT cells. Transplantation of bone marrow from WT animals into miR-155-/- mice partially reverted the effect of ConA on miR-155-/- as assessed by serum transaminases and expression of proinflammatory cytokines. Patients with chronic alcohol and virus C induced liver injury and autoimmune hepatitis have a marked increase of miR-155 expression in liver tissue but a reduced expression of miR-155 in peripheral blood mononuclear cells.
Conclusions: During liver injury, expression of miR-155 is altered in both liver tissue and circulating inflammatory cells, thus regulating inflammatory cell recruitment and liver damage. Our results suggest that maintaining miR-155 expression in inflammatory cells might be a potential therapeutic strategy to mitigate liver injury.
