Chae-Woong Lim

Immune modulatory effects of the foodborne contaminant citrinin in mice.

The mycotoxin citrinin can cause mycotoxic nephropathy, cytotoxicity and genotoxicity. To investigate the immune modulatory effects, CTN was orally administered to female BALB/c mice at the dose of 1, 5, or 10 mg/kg body weight for 14 days, and several immunotoxicity tests were performed. The populations of F4/80+ cells and CD19+ cells were significantly decreased in spleen and MLN. In MLN, CD4+, CD8+, and CD4+CD25+Foxp3+ cell populations were increased. CD8+ cells were increased but CD19+ cells were decreased in intra-epithelial, lamina propria and Peyers patches lymphocytes. In a cell proliferation assay, along with the increased proliferative capacities of ConA-induced splenocytes and MLN cells, IFN-γ production was increased. The expression of TLR 2 was increased in spleen, but TLR 3 expression in MLN was decreased. The level of serum IgM was reduced. Furthermore, apoptosis was induced in spleen, MLN and Peyers patches and promoted by the change in the ratio of Bax/Bcl-2 activities. Autophagy gene Atg5 and Beclin-1 were up-regulated in spleen. The expressions of IL-1β, IL-10, and TNF-α were inhibited in murine macrophage cells pre-exposed with TLR ligands. These results indicate that CTN has multiple immune modulatory effects in mice that may alter normal functions of immune system.

EURASIAN OTTER (LUTRA LUTRA), A DEFINITIVE HOST FOR DIROFILARIA IMMITIS

Abstract A mature male and a mature female Dirofilaria immitis were found in the right ventricle of the heart of a naturally infected 2-yr-old male Eurasian otter (Lutra lutra) that had died of severe lung congestion at a zoo in South Korea. Both developing embryos and microfilariae were present in the uterus of the female D. immitis. Although circulating microfilariae were not detected in blood or tissue, the Eurasian otter may serve as a definitive host for D. immitis.

G-Aminobutyric acid promotes methionine-choline deficient diet-induced nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects. To test this hypothesis, C57BL/6 mice were fed a methionine-choline-deficient (MCD) diet for 8 weeks. After four weeks into MCD feeding, mice were provided with plain water (control) or water containing 2 mg/mL of GABA for the subsequent 4 weeks. Using this MCD diet-induced NASH model, we found that mice receiving GABA showed more severe steatohepatitis and liver fibrosis than control mice. This increased liver damage was confirmed by higher levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) compared to the control group. In accordance with increased liver steatohepatitis, NASH-related and inflammatory gene expression (collagen α1, tissue inhibitor of metalloproteinase-1, TNF-α) in the liver was markedly increased in GABA-treated mice. Furthermore, GABA directly enhanced production of inflammatory cytokines including IL-6 and TNF-α in LPS activated RAW macrophage cells and increased TIB-73 hepatocyte death. Such effects were abolished when GABA was treated with bicuculline, a competitive antagonist of GABA receptors. These results suggest that oral administration of GABA may be involved in changes of the liver immune milieu and conferred detrimental effects on NASH progression.Abstract Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. Γ-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects. To test this hypothesis, C57BL/6 mice were fed a methionine–choline-deficient (MCD) diet for 8 weeks. After four weeks into MCD feeding, mice were provided with plain water (control) or water containing 2 mg/mL of GABA for the subsequent 4 weeks. Using this MCD diet-induced NASH model, we found that mice receiving GABA showed more severe steatohepatitis and liver fibrosis than control mice. This increased liver damage was confirmed by higher levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) compared to the control group. In accordance with increased liver steatohepatitis, NASH-related and inflammatory gene expression (collagen α1, tissue inhibitor of metalloproteinase-1, TNF-α) in the liver was markedly increased in GABA-treated mice. Furthermore, GABA directly enhanced production of inflammatory cytokines including IL-6 and TNF-α in LPS activated RAW macrophage cells and increased TIB–73 hepatocyte death. Such effects were abolished when GABA was treated with bicuculline, a competitive antagonist of GABA receptors. These results suggest that oral administration of GABA may be involved in changes of the liver immune milieu and conferred detrimental effects on NASH progression.