Anti-ARG1 (C-terminal) polyclonal antibody

Objective: To study the therapeutic effect of berberine (BBR) on metabolic syndrome insulin resistance and the impact on macrophage M2 polarization, and to investigate the mechanism of action of BBR. Method: Ten SD rats were in the normal group. The other 40 rats were used to establish the metabolic syndrome model, and were randomly divided into the model group (n=20) and the treatment group (n=20). Rats were fasted overnight, and serum was tested for mRNA levels of M2 marker genes, Mrc1, Ym1, Fizz1, and Arg1. Fasting blood-glucose (FBG) and fasting insulin (FINS) levels were also obtained, and the insulin resistance index (HOMA-IR) was calculated. Results: After treatment, the FBG and FINS levels and the HOMA-IR of rats in treatment group decreased compared with those of the rats in the same group before treatment (P<0.05), and were also significantly lower than those of the rats in the model group (P<0.05). The FBG and FINS levels and HOMA-IR of rats in the treatment group decreased following implementation of the high-fat diet (P<0.05). Moreover, after treatment, mRNA levels of Mrc1, Ym1, Fizz1, and Arg1 of rats in the treatment group increased compared with those before treatment (P<0.05), and also compared with those in the model group (P<0.05). Arg1 was higher in the treatment group than in the normal group (P<0.05), Ym1 and Fizz1 were lower than that in the normal group (P<0.05). Conclusions: BBR improves metabolic syndrome insulin resistance by inducing M2 tissue macrophage polarization.

BackgroundMultiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease characterized by both inflammatory demyelination and impaired remyelination. Studies indicate that Toll-like receptor 2 (TLR2) signaling contributes to both the inflammatory component and the defective remyelination in MS. While most MS therapeutics target adaptive immunity, we recently reported that reducing TLR2 signaling in innate immune cells by inducing TLR2 tolerance attenuates adoptively transferred experimental autoimmune encephalomyelitis. Given that previous reports suggest TLR2 signaling also inhibits myelin repair, the objective of this study was to assess how reducing TLR2 signaling through TLR2 tolerance induction affects CNS myelin repair.MethodsChow containing 0.2% cuprizone was fed to male and female wild-type (WT) C57BL/6 mice or TLR2-deficient (TLR2(-/-)) mice for 5weeks to induce demyelination. During a 2-week remyelination period following discontinuation of cuprizone, WT mice received either low dose TLR2 ligands to induce systemic TLR2 tolerance or vehicle control (VC). Remyelination was evaluated via electron microscopy and immunohistochemical analysis of microglia and oligodendrocytes in the corpus callosum. Statistical tests included 2-way ANOVA and Mann-Whitney U analyses.ResultsInducing TLR2 tolerance in WT mice during remyelination significantly enhanced myelin recovery, restoring unmyelinated axon frequency and myelin thickness to baseline levels compared to VC-treated mice. Mechanistically, enhanced remyelination in TLR2 tolerized mice was associated with a shift in corpus callosum microglia from a pro-inflammatory iNOS(+) phenotype to a non-inflammatory/pro-repair Arg1(+) phenotype. This result was confirmed in vitro by inducing TLR2 tolerance in WT microglia cultures. TLR2(-/-) mice, without TLR2 tolerance induction, also significantly enhanced myelin recovery compared to WT mice, adding confirmation that reduced TLR2 signaling is associated with enhanced remyelination.DiscussionOur results suggest that reducing TLR2 signaling in vivo by inducing TLR2 tolerance significantly enhances myelin repair. Furthermore, the enhanced remyelination resulting from TLR2 tolerance induction is associated with a shift in corpus callosum microglia from a pro-inflammatory iNOS(+) phenotype to a non-inflammatory/pro-repair Arg1(+) phenotype. While deletion of TLR2 would be an impractical approach in vivo, reducing innate immune signaling through TLR2 tolerance induction may represent a novel, two-pronged approach for treating both inflammatory and myelin repair components of MS.