• Biomedical Science Letters
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• v.5 no.1
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• pp.85-93
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• 1999

Nitric oxide (NO) plays an important role in immunologic defense, and influences upon the functioning of secretory tissues and cells. It also exhibits cytotoxic/cytostatic activity as one of major operating effectors of the cellular immunity system. We investigated the effects of serum on the cell damages and NO production in the mouse liver cell line BNL CL.2 to establish the role of NO. We observed that, when BNL CL.2 cells were cultured in serum-free medium, they were induced to cell damage by the stimulation of IFN-$\gamma$ alone or IFN-$\gamma$ plus LPS. Serum-starved cells showed large amount of nitrite accumulation and NO synthase (NOS) expression in response to IFN-$\gamma$ alone in dose- and time- dependent manners, but serum-supplied cells did not The production of NO was blocked by protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin. These results suggest that the deprivation of serum in the BNL CL.2 cell culture medium might primed with the cells to produce NO when the cells are triggered by IFN-$\gamma$ and the involvement of PTK signal transduction pathway in the expression of NOS gene in murine hepatocytes.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1056-1069
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• 2023

BACKGROUND/OBJECTIVES: Grifola frondosa, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin disorders have not been sufficiently elucidated. This study aimed to elucidate the anti-inflammatory role of the ethanol extract of G. frondosa in atopic dermatitis (AD) using in vivo and in vitro models. MATERIALS/METHODS: We investigated its impact on skin and spleen inflammatory responses in Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in a mouse model. Additionally, we determined the immunosuppressive response and mechanism of G. frondosa by inducing atopic-like immune reactions in keratinocytes through tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. RESULTS: Our study revealed that G. frondosa ameliorates clinical symptoms in an AD-like mouse model. These effects contributed to the suppression of Th1, Th2, Th17, and Th22 immune responses in the skin and spleen, leading to protection against cutaneous inflammation. Furthermore, G. frondosa inhibited the production of antibodies immunoglobulin (Ig)E and IgG2a in the serum of AD mice. Importantly, the inhibitory effect of G. frondosa on inflammatory cytokines in TNF-α/IFN-γ-stimulated AD-like keratinocytes was associated with the suppression of MAPK (Mitogen Activated Protein Kinase) pathway activation. CONCLUSIONS: Collectively, these findings highlight the potential of G. frondosa as a novel therapeutic agent for AD treatment and prevention.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.33-41
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• 2005

Objective : The effect of Ulmus davidiana Planch(UD), which has long been known to have anti-inflammation and protective effects on damaged tissue, inflammation and bone among other functions, on the development of type II collagen (CII)-induced arthritis (CIA) in rats was studied. Methods : Male rats were immunized with an emulsion of $200\;{\mu}g$ of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneal stimulation of Ulmus davidiana Planch herbal acupuncture(UDHA)or saline during the experiment. When compared with rats treated with saline as control, UDHA at doses of more than $20{\mu}g/100\;g$ rat once a day for 7 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-2, interleukin-6, $IFN-{\gamma}$ when the cells were obtained from rats 14 days after immunization and cultured in vitro with CII. Results : When rats were injected intraperitoneally, UD -treated group and control group rats did not differ significantly when low doses of UD was given to rats. Conclusion : The recommended dose of UD in the management and treatment of rat CIA will be more than $20{\mu}g/100\;g$, which is two-firth of human therapeutic dose. From the results, it was concluded that the effect of UDHA is dependent of dosage.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.2
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• pp.163-169
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• 2012

Interferon regulatory factor 6 (IRF6) gene is a member of the IRF-family, and plays functionally diverse roles in the regulation of the immune system. In this report, the 13,720 bp porcine IRF6 genomic DNA structure was firstly identified with a putative IRF6 protein of 467 amino acids. Alignment and phylogenetic analysis of the porcine IRF6 amino acid sequences with their homologies to other species showed high identity (over 96%). Tissues expression of IRF6 mRNA was observed by RT-PCR, the results revealed IRF6 expressed widely in eight tissues. One SNP (HQ026023:1383 G>C) in exon7 and two SNPs (HQ026023:130 G>A; 232 C>T) in the 5′ promoter region of porcine IRF6 gene were demonstrated by DNA sequencing analysis. A further analysis of SNP genotypes associated with immune traits including IFN-${\gamma}$ and IL10 concentrations in serum was carried out in three pig populations including Large White, Landraces and Songliao Black pig (a Chinese indigenous breed). The results showed that the SNP (HQ026023:1383 G>C) was significantly associated with the level of IFN-${\gamma}$ (d 20) in serum (p = 0.038) and the ratio of IFN-${\gamma}$ to IL10 (d 20) in serum (p = 0.041); The other two SNPs (HQ026023:130 G>A; 232 C>T) were highly significantly associated with IL10 level in serum both at the day 20 (p = 0.005; p = 0.001) and the day 35 (p = 0.004; p = 0.006). Identification of the porcine IRF6 gene will help our further understanding of the molecular basis of the IFN regulation pathway in the porcine immune response. All these results should indicate that the IRF6 gene can be regarded as a molecular marker associated with the IL10 level in serum and used for genetic selection in the pig breeding.

• YAKHAK HOEJI
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• v.50 no.3
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• pp.184-190
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• 2006

We investigated the effect of fresh Rehmanniae radix methanol extracts (RGMeOH) on the in vitro production of cytokines by splenocytes and peritoneal macrophages isolated from C57BL/6 mice. Peritoneal macrophages and splenocytes were incubated with various concentrations of RGMeOH in the presence of $10\;{\mu}g/ml$ of lipopolysaccharide (LPS) $1\;{\mu}g/ml$ of concanavalin A (Con A) for cytokine assay, These results showed that RGMeOH remarkably attenuated LPS-increased production of $TNF-{\alpha}$ but not IL-6 by peritoneal macrophages and enhanced LPS-stimulated production of IL-10 in a dose-dependent manner RGMeOH significantly augmented the LPS- or Con A-stimulated production of IL-2 and $IFN-{\gamma}$ by splenocytes. These findings suggest that RGMeOH may attenuate inflammatory responses through down-regulation of $TNF-{\alpha}$ and up-regulation of IL-10, and that RGMeOH may up-regulate cell-mediated immune responses through increase in IL-2 and $IFN-{\gamma}$ production.

• The Journal of Internal Korean Medicine
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• v.20 no.1
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• pp.73-82
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• 1999

Nitric oxide (NO) is now recognized as a mediator of several biological and immunological functions, but unlike classical neurotransmitters. NO simply diffuse of the postsynaptic cells and around affecting cells. Taraxacum officinale (Compositae) has been used for maintenance of vitality, and they still occupy an important place in the traditional Korean medicine. We have examined that the effect of Taraxacum officinale water extract on NO synthesis in microglial cells of murine's brain, using the Griess method. And this study was evident that Taraxacum officinale did not induce NO production without recombinant interferon gamma ($rIFN-{\gamma}$), whereas Taraxacum officinale (10-1000 g/ml) with $rIFN-{\gamma}$ effectively produced NO in microglial cells of brain. As result. NO production in microglial cells increased most significantly in dose of 100 g/ml of the Taraxacum officinale and the production of NO was dependent on the dose of Taraxacum officinale, NG-monomethyl-L-arginine, competitive inhibitor of NO synthase, reduced the NO production by Taraxacum officinale stimulation with $rIFN-{\gamma}$ in microglial cells of murine. The effect of Taraxacum officinale was mainly dependent on Taraxacum officinale-induced tumor necrosis factor- secretion. Conclusively, this study suggested that Taraxacum officinale stimulate NO production at microglial cells in brain, which may be an important factor for mediating immune and neuroendocrinologic regulation in nervous system.

• Parasites, Hosts and Diseases
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• v.55 no.3
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• pp.295-304
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• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• The Korean Journal of Food And Nutrition
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• v.31 no.2
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• pp.236-241
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• 2018

Flammulina velutipes is an edible mushroom and contains a lot of fiber, vitamin $B_1$, $B_2$, niacin and folic acid. This study was conducted to explore the effects of the Flammulina velutipes mushroom on immune cells and immunity. Th1 cytokine productions as $IFN-{\gamma}$, $TNF-{\alpha}$, and IL-2 were measured in an activated macrophage by Flammulina velutipes water extract in seven concentrations (0, 5, 10, 50, 100, 250, 500, and $1,000{\mu}g/mL$). Also, the splenocyte proliferation index was measured at 48 hours after treatment of the Flammulina velutipes water extract in seven concentrations or mitogen, LPS and ConA. The $IFN-{\gamma}$ and $TNF-{\alpha}$ productions were increased by treatment of the Flammulina velutipes water extract. The $TNF-{\alpha}$ production was significantly higher in the $50{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extract treated macrophages. The $IFN-{\gamma}$ production of macrophages treated with the Flammulina velutipes water extract increased significantly in all groups, and the highest $1000{\mu}g/mL$ concentration. The splenocyte proliferation index was enhanced when the $10{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extracts were treated compared to the control. These primary results suggest that Flammulina velutipes may enhance the immune function by activation of the macrophage and spleen cell.

• Korean Journal of Plant Resources
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• v.21 no.4
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• pp.336-340
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• 2008

Corilagin (CRN) isolated from Euphorbia helioscopia as rheumatoid arthritis drug. CRN was medicated to the abdominal cavity of collagen induced arthritis (CIA) mice that was an animal model for rheumatoid arthritis and its effects on incidence and arthritis index were studied. The results were as folllows; It was exhibited that medicating corilagin inhibited the infiltration of activated T lymphocytes into an inflammatory joint. The production of IgG and IgM that were RF (rheumatoid factor) and inflammatory cytokine, IL-6 and $TNF-{\alpha}$were reduced. After measuring $IFN-{\gamma}$and IL-4, it was found that it was shifted into Th2 immune response as increasing in IL-4. After liver function test, studies on liver poisoning of AST/ALT should be continued.

• Journal of Acupuncture Research
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• v.36 no.4
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• pp.256-263
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• 2019

Background: The purpose of this study was to investigate the anti-inflammatory response of lipopolysaccharide (LPS) activated macrophages (RAW 264.7 murine cell line) to JCE003 which is an extract including Eucommia ulmoides, Juglans regia, Eleutherococcus senticosus, and Zingiber officinale. Methods: An MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] assay was performed to analyze the survival rate of RAW 264.7 cells. The production of nitric oxide and pro-inflammatory cytokines (IFN-${\gamma}$, TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in LPS-induced RAW 264.7 cells was measured by enzyme-linked immunosorbent assay. mRNA expression levels of pro-inflammatory cytokines (IFN-${\gamma}$, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) were analyzed by quantitative polymerase chain reaction analysis. Results: Exposure of LPS-activated RAW 264.7 cells to JCE003 was not cytotoxic up to $400{\mu}g/mL$, but cell survival was statistically significantly decreased at $800{\mu}g/mL$ (p < 0.001). Nitric oxide production was not markedly lowered in LPS-activated RAW 264.7 cells by exposure to JCE003 (10, 50, 100, 200, 400, $800{\mu}l/mL$) compared with the Control group. In addition, JCE003 reduced the production of TNF-${\alpha}$ in LPS-induced RAW 264.7 cells at $400{\mu}g/mL$ (p < 0.05), but IFN-${\gamma}$ and TNF-${\alpha}$ mRNA expression in LPS-induced RAW 264.7 cells was decreased at 100, 200, and $400{\mu}g/mL$ JCE003 (p < 0.01). Conclusion: These results suggest that JCE003 inhibited the expression and production of pro-inflammatory cytokines in LPS-activated RAW 264.7 cells. The findings of this study provide basic data for the development of new Korean medicine anti-inflammatory drugs.