M1-and M2-macrophage polarization in rat liver cirrhosis induced by thioacetamide (TAA), focusing on Iba1 and galectin-3

Introduction: Resident and exudate macrophages play an important role in the development of liver cirrhosis. Ionized calcium binding adaptor molecule 1(+) (Ibal(+)) and gated-in-3-F (Gal-3(+)) macrophages regulate liver fibrosis probably through pro-inflammatory and pro-fibrotic factors. Macrophages show polarized functions in liver fibrosis; however, M1-/M2-polarization of lba1(+) and Gal-3(+) macrophages remains obscured. This study investigated the M1-/M2-polarized properties of lbal(+) and Gal-3(+) macrophages in chemical-induced liver cirrhosis. Materials and methods: Cirrhosis was induced in F344 rats by repeated injections of thioacetamide (100 mg/kg BW, twice a week for 25 weeks). Liver samples were collected from post-first-injection (PFI) week 5 to 25. Macrophage immunophenotypes and myofibroblasts in the fibrous bridges (FBs) and pseudolobules (PLs) were analyzed by immunohistochemistry. Expressions of Ml- and M2-related factors were analyzed with RT-PCR, separately in FBs and PLs. Results: Activation of myofibroblasts was most pronounced in livers at week 15. CD68(+) (M1), CD204(+) (M2), lbal(+) and Gal-3(+) macrophages in the FBs increased gradually and peaked at week 15, consistent with the upregulation of both M1-(MCP-1, IFN-gamma, IL-1 beta, IL-6, and TNF-alpha) and M2-(TGF-beta 1, IL-4, and IL-10) related factors. Iba1(+) and Gal-3(+) macrophages showed both Ml- and M2-immunophenotypes. CD163(+) macrophages showed a persistent increase, consistent with TGF-beta 1 upregulation. MHC class II+ macrophages increased in the developing fibrotic lesions, and then reduced in the advanced stage cirrhosis. Conclusion: Both Ml- and M2-macrophage polarizations occur during development of liver cirrhosis. lbal(+) and Gal-3(+) macrophages participate in liver cirrhosis through production of both MI- and M2-related factors. (c) 2014 Elsevier Inc. All rights reserved.