• IMMUNE NETWORK
• /
• v.13 no.6
• /
• pp.249-256
• /
• 2013

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

• Journal of Microbiology
• /
• v.45 no.4
• /
• pp.364-366
• /
• 2007

The immunological role of the Pasteurella multocida toxin (PMT) in mice was examined using a PMT mutant strain. After a nasal inoculation, the mutant strain failed to induce interstitial pneumonia. Moreover, PMT had no significant effect on the populations of CD4+, CD8+, CD3+, and CD19+ immunocytes in blood or on the populations of CD4+ and CD8+ splenocytes (P<0.01). However, there was a significant increase in the total number of cells in the BAL samples obtained from the wild-type P. multocida-inoculated mice. On the other hand, the level of IL-l expression decreased when the macrophages from the bronchio-alveolar lavage were stimulated with PMT. Overall, PMT appears to play some role (stimulating and/or inhibiting) in the immunological responses but further studies will be required to confirm this.

• Progress in Medical Physics
• /
• v.21 no.2
• /
• pp.209-217
• /
• 2010

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Since retinal prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. Therefore, in this paper, we focused on retinal ganglion cell (RGC) responses to different voltage stimulation parameters and compared threshold charge densities in normal and rd1 mice. For this purpose, we used in vitro preparation for the retina of normal and rd1 mice on micro-electrode arrays. When the neural network of rd1 mouse retinas is stimulated with voltage-controlled pulses, RGCs in degenerated retina also respond to voltage amplitude or voltage duration modulation as well in wild-type RGCs. But the temporal pattern of RGCs response is very different; in wild-type RGCs, single peak within 100 ms appears while in RGCs in degenerated retina multiple peaks (~4 peaks) with ~10 Hz rhythm within 400 ms appear. The thresholds for electrical activation of RGCs are overall more elevated in rd1 mouse retinas compared to wild-type mouse retinas: The thresholds for activation of RGCs in rd1 mouse retinas were on average two times higher ($70.50{\sim}99.87\;{\mu}C/cm^2$ vs. $37.23{\sim}61.65\;{\mu}C/cm^2$) in the experiment of voltage amplitude modulation and five times higher ($120.5{\sim}170.6\;{\mu}C/cm^2$ vs. $22.69{\sim}37.57\;{\mu}C/cm^2$) in the experiment of voltage duration modulation than those in wild-type mouse retinas. This is compatible with the findings from human studies that the currents required for evoking visual percepts in RP patients is much higher than those needed in healthy individuals. These results will be used as a guideline for optimal stimulation parameters for upcoming Korean-type retinal prosthesis.

• Korean Journal of Food Science and Technology
• /
• v.33 no.6
• /
• pp.795-801
• /
• 2001

Effects of Mucilage fraction from Yam (Dioscorea batatas DECENE), which has long been used as a wild vegetable and folk medicine, on blood glucose and lipid composition in alloxan-induced diabetic mice were investigated. Diabetes mellitus was induced in male ICR mice by the injection of alloxan into the tail vein at a dose of 75 mg/kgBW. Alloxan-induced diabetic mice were administered the yam mucilage fraction1 orally ; y500F1 group (500 mg/kgBW/day fraction1) and y750F1 group (750 mg/kgBW/day fraction1); and the normal and alloxan-control group were orally administered with saline for 10 days. The body weight gain and food intake were monitored every day. The concentrations of glucose, triglyceride, total cholesterol, and LDL-cholesterol of serum and liver levels of glucose, triglyceride, and cholesterol were determined. Also weight of liver, heart, spleen and kidney were measured. The fraction 1 of yam mucilage lowered body weight gain significantly (p<0.05) and decreased serum glucose levels in alloxan-induced diatetic mice compared to that of alloxan-control group. In alloxan induced diabetic mice serum triglyceride level was lowered and liver HDL-cholesterol level increased significantly (p<0.05). In conclusion, it was assumed that yam mucilage fraction 1 has anti-hyperglycemic and anti-obesitic effects by reducing body weight gain and decreasing serum glucose and triglyceride level.

• Journal of Ginseng Research
• /
• v.46 no.4
• /
• pp.561-571
• /
• 2022

Background: Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin. Methods: 3T3-L1 adipocytes and hepatocytes were used to investigate GRb1's action on adiponectin expression and triglyceride (TG) accumulation. Wild type (WT) mice and adiponectin knockout (KO) mice fed high fat diet were treated with GRb1 for 2 weeks. Hepatic fat accumulation and function as well as insulin sensitivity was measured. The activation of AMPK was also detected in the liver and hepatocytes. Results: GRb1 reversed the reduction of adiponectin secretion in adipocytes. The conditioned medium (CM) from adipocytes treated with GRb1 reduced TG accumulation in hepatocytes, which was partly attenuated by the adiponectin antibody. In the KO mice, the GRb1-induced significant decrease of TG content, ALT and AST was blocked by the deletion of adiponectin. The elevations of GRb1-induced insulin sensitivity indicated by OGTT, ITT and HOMA-IR were also weakened in the KO mice. The CM treatment significantly enhanced the phosphorylation of AMPK in hepatocytes, but not GRb1 treatment. Likewise, the phosphorylation of AMPK in liver of the WT mice was increased by GRb1, but not in the KO mice. Conclusions: The up-regulation of adiponectin by GRb1 contributes to the amelioration of liver steatosis and insulin resistance, which further elucidates a new mechanism underlying the beneficial effects of GRb1 on obesity.

• Journal of Ginseng Research
• /
• v.45 no.6
• /
• pp.665-675
• /
• 2021

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.376-384
• /
• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Journal of Ginseng Research
• /
• v.47 no.4
• /
• pp.561-571
• /
• 2023

Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

• IMMUNE NETWORK
• /
• v.20 no.5
• /
• pp.40.1-40.15
• /
• 2020

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM-19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.

• Korean Journal of Veterinary Research
• /
• v.53 no.4
• /
• pp.217-224
• /
• 2013

Transgenic plants have been tested as an alternative host for the production and delivery of experimental oral vaccines. Here, we developed transgenic potatoes that express the major antigenic sites A and D of the glycoprotein S from transmissible gastroenteritis coronavirus (TGEV-$S_{0.7}$) under three expression vector systems. The DNA integration and mRNA expression level of the TGEV-$S_{0.7}$ gene were confirmed in transgenic plants by PCR and northern blot analysis. Antigen protein expression in transgenic potato was determined by western blot analysis. Enzyme-linked immunosorbent assay results revealed that based on a dilution series of Escherichia coli-derived antigen, the transgenic line P-2 had TGEV-$S_{0.7}$ protein at levels that were 0.015% of total soluble proteins. We then examined the immunogenicity of potato-derived TGEV-$S_{0.7}$ antigen in mice. Compared with the wild-type potato treated group and synthetic antigen treated group, mice treated with the potato-derived antigen showed significantly higher levels of immunoglobulin (Ig) G and IgA responses.