Background & Aims: BALB/c mice have been shown to easily induce Th2 type responses in several infection models. Certain macrophage phenotypes contribute to liver fibrosis. Upon injury the changing tissue microenvironment alters their phenotype and primes infiltrating monocytes toward pro-inflammatory macrophages. Here, we characterized changes in macrophages phenotype (M1/M2) during fibrogenesis in a mice model of liver fibrosis.

Methods: Carbon-tetrachloride (CCl₄) hepatic-fibrosis was induced in Balb/c-mice for 4 weeks through i.p injections/2x week. Along 1th to 4th weeks liver macrophages were isolated and were identified by the flow cytometry as CD45+/CD16+/CD68+.  M1/M2 model of macrophage polarization was determined by CD80/CD273 (programmed death ligand 2 (PDL2)), respectively. Liver proteins were quantified for aSMA expressions by western blot and RT PCR, respectively. Livers were also assessed histologically and serum ALT levels were estimated.

Results: Hepatic fibrosis were gradually increased along 4 weeks injections of CCl₄ as indicated by serum ALT levels and aSMA expressions (P<0.02) as well as H&E staining of liver necro-inflammatory lesions. These results were associated with increase in liver CD273 (M2 macrophage subpopulation) expressions (from 20.1%± 3.1in naïve mice to 27.8%±3.2 in fibrotic mice; P=0.01), however, no significant changes were observed between the mice groups of the different changes in fibrosis severity. On the other hand, gradual decrease in CD80 expressions (M2 macrophage subpopulation) were seen along fibrosis progressions (From 12%±6.2 in naïve mice to 1.97%±0.4 in fibrotic mice; P<0.02). The overall data showed a decrease in M1/M2 macrophage ratio in BALB/c mice model of liver fibrosis indicating a reduced differentiation of M1 macrophages. These results were accompanied with inhibited expressions in M2 macrophages IFN-g and IL-12 while high levels of TGF-b.

Conclusion: The known anti-inflammatory M2 macrophages were predominated prior and during liver injury. Although they were elevated by count during fibrosis, they secreted less IFN-g and IL-12 which might indicate inability of differentiation of naive T- cells into Th1 cells. Our data could suggest pro-fibrotic role of M2 macrophages through their productions of TGF-b with reduced M1 pro-inflammatory macrophages.

Conference Title

EASL-Paris

Conference Country

France

Conference Date

April 11, 2018 - April 15, 2018

Conference Sponsor

EASL

Additional Info

Conference Website