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

Abstract

IntroductionResident and exudate macrophages play an important role in the development of liver cirrhosis. Ionized calcium binding adaptor molecule 1+ (Iba1+) and galectin-3+ (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 Iba1+ and Gal-3+ macrophages remains obscured. This study investigated the M1-/M2-polarized properties of Iba1+ and Gal-3+ macrophages in chemical-induced liver cirrhosis. Materials and methodsCirrhosis was induced in F344 rats by repeated injections of thioacetamide (100mg/kg BW, twice a week for 25weeks). 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 M1- and M2-related factors were analyzed with RT-PCR, separately in FBs and PLs. ResultsActivation of myofibroblasts was most pronounced in livers at week 15. CD68+ (M1), CD204+ (M2), Iba1+ and Gal-3+ macrophages in the FBs increased gradually and peaked at week 15, consistent with the upregulation of both M1-(MCP-1, IFN-γ, IL-1β, IL-6, and TNF-α) and M2-(TGF-β1, IL-4, and IL-10) related factors. Iba1+ and Gal-3+ macrophages showed both M1- and M2-immunophenotypes. CD163+ macrophages showed a persistent increase, consistent with TGF-β1 upregulation. MHC class II+ macrophages increased in the developing fibrotic lesions, and then reduced in the advanced stage cirrhosis. ConclusionBoth M1- and M2-macrophage polarizations occur during development of liver cirrhosis. Iba1+ and Gal-3+ macrophages participate in liver cirrhosis through production of both M1- and M2-related factors.