• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.279-288
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• 2002

This research investigates the effect of the Crataegus pinnatifida BGE. var. major N.E. BR(CPVM) on Alzheimer's disease. The CPVM extract suppressed the expression of IL-1 β, IL-6, APP, AChE mRNA in PC-12 cells treated with CT105. The CPVM extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT105. The CPVM extract group showed a significant inhibitory effect on the memory deficit for the mice with Alzheimer's disease induced by CT105 in the Morris water maze experiment. The CPVM extract suppressed the over-expression of IL-1 β, TNF- α and ROS in the mice with Alzheimer's disease induced by CT105. This study suggests that CPVM may be effective for the prevention and treatment of Alzheimer's disease.

• BMB Reports
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• v.49 no.4
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• pp.232-237
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• 2016

Mulberry tree twigs (Ramulus mori) contain large amounts of oxyresveratrols and have traditionally been used as herbal medicines because of their anti-inflammatory properties. However, the signaling mechanism by which R. mori exerts its anti-inflammatory action remains to be elucidated. In this study, we observed that R. mori ethanol extracts (RME) exerted an inhibitory effect on the lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokine interleukin-6 (IL-6) in Raw264.7 macrophage cells. Additionally, RME inhibited IL-6 production by blocking the leukotriene B₄ receptor-2 (BLT2)-dependent-NADPH oxidase 1 (NOX1)-reactive oxygen species (ROS) cascade, leading to anti-inflammatory activity. Finally, RME suppressed the production of the BLT2 ligands LTB4 and 12(S)-HETE by inhibiting the p38 kinase-cytosolic phospholipase A₂-5-/12-lipoxygenase cascade in LPS-stimulated Raw264.7 cells. Overall, our results suggest that RME inhibits the 'BLT2 ligand-BLT2'-linked autocrine inflammatory axis, and that this BLT2-linked cascade is one of the targets of the anti-inflammatory action of R. mori.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.117-121
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• 2017

We have previously shown that the specific phosphatidylinositol 3-kinase inhibitor LY294002 (LY29), and its inactive analog LY303511 (LY30), inhibit a monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells; these results suggest the potential of LY30 as an anti-inflammatory drug. In this study, we determined the effects of LY30 on the production of various inflammatory cytokines in human macrophagic THP-1 cells which were stimulated with lipopolysaccharide (LPS). LY30 selectively suppressed the mRNA expression of IL-12 p40, $TNF-{\alpha}$, and MCP-1 without affecting the expression of $IL-1{\alpha}$, IL-6, and IL-8. Inhibition of the production of IL-12 and $TNF-{\alpha}$ by LY30 was also demonstrated using ELISA assays. In order to elucidate the mechanisms of the action of LY30, we examined the role played by the mitogen-activated protein kinases and the key transcription factors, AP-1 and $NF-{\kappa}B$ in LPS-stimulated THP-1 cells. The results revealed that LY30 inhibited LPS-induced activation of ERK, but not p38 or JNK. Furthermore, the AP-1 DNA binding activity was suppressed by LY30 based upon the dosage, whereas $NF-{\kappa}B$ DNA binding was not affected. These results suggest that LY30 selectively inhibits cytokine production in the LPS-stimulated macrophagic THP-1 cells by down-regulating the activation of ERK and AP-1.

• Food Science of Animal Resources
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• v.42 no.5
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• pp.903-914
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• 2022

Probiotics are currently considered as one of tools to modulate immune responses under specific clinical conditions. The purpose of this study was to evaluate whether oral administration of three different probiotics (Lactiplantibacillus plantarum CJLP243, CJW55-10, and CJLP475) could evoke a cell-mediated immunity in immunodeficient mice. Before conducting in vivo experiments, we examined the in vitro potency of these probiotics for macrophage activation. After co-culture with these probiotics, bone marrow derived macrophages (BMDMs) produced significant amounts of proinflammatory cytokines including interleukin-6 (IL-6), IL-12, and tumor necrosis factor-α (TNF-α). Levels of inducible nitric oxide synthase (inos) and co-stimulatory molecules (CD80 and CD86) were also upregulated in BMDMs after treatment with some of these probiotics. To establish an immunocompromised animal model, we intraperitoneally injected mice with cyclophosphamide on day 0 and again on day 2. Starting day 3, we orally administered probiotics every day for the last 15 d. After sacrificing experimental mice on day 18, splenocytes were isolated and co-cultured with these probiotics for 3 d to measure levels of several cytokines and immune cell proliferation. Results clearly indicated that the consumption of all three probiotic strains promoted secretion of interferon-γ (IFN-γ), IL-1β, IL-6, IL-12, and TNF-α. NK cell cytotoxicity and proliferation of immune cells were also increased. Taken together, our data strongly suggest that consumption of some probiotics might induce cell-mediated immune responses in immunocompromised mice.

• Journal of Hospice and Palliative Care
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• v.6 no.1
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• pp.51-57
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• 2003

Purpose : Anorexia-cachexia syndrome is one of the most common symptoms and main cause of death in terminal cancer patients. This symptom is due to the enlarged cancer mass as well as tumor released cytokines. Some doctors have suggested that vitamin C was preferentially toxic to tumor cells in vitro and in vivo, and improved clinical symptoms in terminal cancer patients. Therefore, we measured cytokines in serum of terminal cancer patients to determine whether vitamin C treatment improved the anorexia-cachexia syndrome. Methods : We investigated that 49 terminal cancer patients admitted to the department of family medicine, National Health Insurance Corporation Ilsan hospital from March 1, 2002 to August 31, 2002. The study was done on 22 patients who were given 10 g/day of vitamin C infusions during 1 week and 27 patients who were not infused. We measured the cytokines levels ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) before and after 1 week between terminal cancer patients treated vitamin C and without vitamin C. Results : Out of 49 patients, patents treated with vitamin C infusions were 22 (12 male, 10 female), and these without vitamin C were 27 (18 male, 9 female). In patients treated with vitamin C, $IL-1{\beta}\;were\;6.19{\pm}5.17$ before day and $8.76{\pm}5.72$ after 1 week, IL-6 were $3.07{\pm}8.09$ before day and $1.31{\pm}2.36$ after 1 week, and $TNF-{\alpha}\;were\;2.74{\pm}14.24$ before day and $0.50{\pm}2.00$ after 1 week. In patients treated without vitamin C, $IL-1{\beta}\;were\;2.50{\pm}3.58$ before day and $6.49{\pm}12.01$ after 1 week, IL-6 were $1.00{\pm}2.19$ before day and $17.16{\pm}81.55$ after 1 week, and $TNF-{\alpha}\;were\;1.19{\pm}2.98$ before day and $1.27{\pm}1.52$ after 1 week. The level of cytokines in patients treated with vitamin C decreased more than those without vitamin C. However, this represented no statistical value (P=0.0598 in $IL-1{\beta}$, P=0.1664 in IL-6, and P=0.5395 in $TNF-{\alpha}$). Conclusion : In terminal cancer, even if there was no statistical difference in the cytokines levels between patients treated with vitamin C and those not treated, those who were treated had a decrease all cytokines levels. Vitamin C is very safe with almost no side effects. Therefore, vitamin C treatment in terminal cancer patients can be seen as beneficial and helpful for clinical symptoms.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.281-286
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• 2008

Although the interaction between gp130 and the ErbB family has frequently been shown in cancer cells, the mechanism of this interaction remains unclear and controversial. In the present study, we found that specific tyrphostin inhibitors of ErbB2 (AG825 and AG879), but not ErbB1 inhibitor (AG1478), suppressed IL-6-induced tyrosine phosphorylation of STAT3 in schwannoma cells. However, biochemical evidence for transactivation of ErbB2 by IL-6 was not observed. Additionally, the inhibition of ErbB2 expression, with either a specific RNAi or transfection of an ErbB2 mutant lacking the intracellular domain did not inhibit the IL-6-induced tyrosine phosphorylation of STAT3. Thus, it seems that tyrphostins, which are known as specific inhibitors of the ErbB2 kinase, may have non-specific suppressive effects on the IL-6/STAT3 pathway.

• Journal of Yeungnam Medical Science
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• v.40 no.4
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• pp.435-441
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• 2023

Pheochromocytomas and paragangliomas (PPGLs) may secrete hormones or bioactive neuropeptides such as interleukin-6 (IL-6), which can mask the clinical manifestations of catecholamine hypersecretion. We report the case of a patient with delayed diagnosis of paraganglioma due to the development of IL-6-mediated systemic inflammatory response syndrome (SIRS). A 58-year-old woman presented with dyspnea and flank pain accompanied by SIRS and acute cardiac, kidney, and liver injuries. A left paravertebral mass was incidentally observed on abdominal computed tomography (CT). Biochemical tests revealed increased 24-hour urinary metanephrine (2.12 mg/day), plasma norepinephrine (1,588 pg/mL), plasma normetanephrine (2.27 nmol/L), and IL-6 (16.5 pg/mL) levels. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT showed increased uptake of FDG in the left paravertebral mass without metastases. The patient was finally diagnosed with functional paraganglioma crisis. The precipitating factor was unclear, but phendimetrazine tartrate, a norepinephrine-dopamine release drug that the patient regularly took, might have stimulated the paraganglioma. The patient's body temperature and blood pressure were well controlled after alpha-blocker administration, and the retroperitoneal mass was surgically resected successfully. After surgery, the patient's inflammatory, cardiac, renal, and hepatic biomarkers and catecholamine levels improved. In conclusion, our report emphasizes the importance of IL-6-producing PPGLs in the differential diagnosis of SIRS.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.2
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• pp.13-34
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• 2007

Objectives The purpose of this study is to examine of the effect of SPAR medicines on the atopy eruption control Methods This experiment is about the expression of IgE, IL-4, IL-6, IL_13, IgM, IgG2a, IgG2b, IgG1 level in serum, and $IFN-{\gamma}$ production by SPAR medicines. We assayed for $CD3e^+/CD69^+$, $CD044^+/CD19^+$ positive cells by flow cytometry in splenocytes and observed the revelation of $CD3e^+/CD69^+$, $CD4^+/CD8^+$, $CD44^+/CD19^+$ marker in PBMC, spleen and DLN. We also observed the outturn of IL-4, IL-5, CCR3, $IFN-{\gamma}$ in skin of a NC/Nga mice. We also analyzed NC/Nga mice's ear and neck-back skin after biopsy and dye by H&E staining method, measured about epidermis and dermis part in comparison with control group. Results SPAR medicines as treatment result to a NC/Nga mice, clinical skin severity score decreased remarkably than the ontrol group. Specially, experiment was results by measuring IgE and IL-6 content in serum 8 weeks, 10 weeks, 12 weeks, 16 weeks, 20 weeks respectively, and it was decreased remarkably than the control group. After experiment ended, the result that observed the revelation CD3e, CD4, CD8, CD19, CD69, CD11a marker in lymph node establishment were observed and that B/T rate becomes recover as normal with political background. In addition to that, the control group was decreased in the measured value of IL-4, IL-5, IL-13, IgM, IgG2a, IgG1's level in serum, and $IFN-{\gamma}$' production secreted in Th1 cell displayed increase by SPAR medicines. IL-4, IL-5, CCR3, and $IFN-{\gamma}$'s gene revelation amount displayed marked decrease than the control group in result that observe effect that get in skin of a NC/Nga dermatitis mouse. Moreover in culture supernatant which cultivate for 14 days after separate skin cell, IL-13 and IL-6 production, and $CD69^+/CD3e^+$, $CD44^+/CD19^+$ expression cell number was decreased than the control group's number. Course inflammation immunocyte permeated of result that effect that SPAR medicines get to NC/Nga mice's skin establishment analyzes ear and neck-back skin after biopsy, and dye by H&E method decreased about epidermis and inflammation of dermis part remarkably than the control group. Conclusions Th1 cell and Th2 cell observe to be shifted by secretion amount of IL-4 and $IFN-{\gamma}$ by SPAR medicines could know that SPAR medicines can be use for treatung allergy autoimmune disease.

• IMMUNE NETWORK
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• v.12 no.5
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• pp.217-221
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• 2012

Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.267-270
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• 2003

Oleanolic acid is a triterpenoid compound that exists in Oldenlandia diffusa. Recently, oleanolic acid has been noted for antitumor effect. Application of both plant growth regulators, 2,4-D and kinetin, was found to be essential for the induction of callus and suspension cells. Optimum induction condition for callus and suspension cells of Oldenlandia diffusa was determined to be 0.5 mg/L 2,4-D and 0.1 mg/L kinetin. Chromatographic separation of oleanolic acid from its derivatives was achieved using Rexchrom S5-100-ODS column. The retention time of oleanolic acid was 12.6 min and the specific content of oleanolic acid was 0.41 mg/g dry weight.