Abstract

Background: BALB/c mice showed easily induced Th2-type responses in several infection models. Certain macrophage phenotypes contribute to liver fibrosis

Aim: We characterized changes in macrophages phenotype (M1/M2) during fibrogenesis in liver fibrosis mice model.

Methods: Carbon-tetrachloride (CCl4) hepatic-fibrosis was induced in BALB/c mice. Liver macrophages isolated were identified for M1 and M2 by CD80/iNOS and CD273 (programmed death ligand 2 (PDL2)/CD206, respectively. IL-4 were induced i.p along week-2 to week-4 of CCl4. Liver proteins were assessed for SMA expressions, histology and ALT levels.

Results: CCl4-induced hepatic-fibrosis showed increased CD273 (from 20.1%± 3.1in naïve mice to 27.8%±3.2 in fibrotic mice; P=0.01) while gradual decrease in CD80 (from 12%±6.2 in naïve mice to 1.97%±0.4 in fibrotic mice; P<0.02). The overall data showed decreased M1/M2 ratio. M2-macrophages showed inhibited expressions of IFN-, IL-12 and vitamin-D-receptor (VDR) while high TGF- levels. ALT, H&E staining intensities and SMA showed gradually increased along fibrosis while metabolic markers of serum insulin, vitamin D and VDR decreased. IL-4 inductions while inhibited fibrosis it elevated metabolic markers.

Conclusion: M2-macrophages express less IFN- and IL-12, which might indicate inability differentiation of naive T cells into Th1 cells. IL-4 has an anti-fibrotic effect through antagonize M2- macrophages of TGF- and ameliorating insulin, vitamin D, VDR and consequently attenuated liverfibrosis.

Keywords: LAS: Liver injury; Wound healing; Macrophages; Vitamin D receptor