• Bulletin of the Korean Chemical Society
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• v.35 no.11
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• pp.3307-3312
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• 2014

The anti-inflammatory effect of a tubulin inhibitor, N-(5-benzyl-1,3-thiazol-2-yl)-3-(furan-2-yl)prop-2-enamide (1), on innate immune responses remains unclear. Thus, we investigated the effect of 1 on the immune responses mediated by lipopolysaccharide (LPS). The in vitro addition of 1 to dendritic cells and macrophages dose-dependently reduced tumor necrosis factor alpha production elicited by LPS stimulation. Additionally, the stimulation of natural killer (NK) and natural killer T (NKT) cells with 1 resulted in the decrease of interferon gamma ($IFN{\gamma}$) induced by LPS treatment. Moreover, 1 substantially reduced interleukin 12 in dendritic cells (DC) as well as $IFN{\gamma}$ in NKDCs induced by LPS in vitro. Furthermore, the in vivo administration of 1 ameliorated LPS/D-galactosamine-induced endotoxic lethality in mice. Taken together, our results demonstrate for the first time that 1 possesses anti-inflammatory properties, most notably by modulating LPS-induced innate immune responses. Therefore, 1 might have therapeutic potential for the treatment of inflammation-mediated diseases such as sepsis.

• Biomedical Science Letters
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• v.20 no.4
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• pp.194-200
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• 2014

Ginsan, polysaccharide isolated from the root of Panax ginseng C.A. Meyer, has been shown to be a potent immunomodulator, producing several cytokines and stimulating lymphoid cells to proliferate. In this study, ginsan was orally inoculated into BALB/c mice up to 39 days and the activity of immune cells containing macrophages and T cells was analyzed. Moreover, the production of cytokines, e.g., tumor necrotic factor-${\alpha}$ (TNF-${\alpha}$), interferon-${\gamma}$ (IFN-${\gamma}$), GM-CSF and IL-12 was also analyzed. In results, the phagocytosis of macrophages was increased. About 13% cytotoxicity of NK cells was observed in 22 days and 29 days of administration. But, oral administration did not highly affect the proliferation of T cells. In cytokine analysis, 150 mg/kg and 300 mg/kg at 22 days and 29 days showed three times more increase in TNF-${\alpha}$ than the controls. IFN-${\gamma}$ showed 1.07 and 1.16 times more increase at 150 mg/kg and 300 mg/kg over 22 days, respectively more than the controls. 32 days of 150 mg/kg and 300 mg/kg induced GM-CSF of about 1.3 times more than the controls. IL-12 was not induced in samples more than the controls. Ginsan could be a potential immunostimulator. Therefore, our study suggests that it can be adapted as an immunostimulator that requires a relatively short oral administration.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4415-4420
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• 2016

We aimed to investigate any association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL) in the view of cytokines that control inflammation/angiogenesis and their correlation with certain CD markers. NHL patients with or without HCV infection were studied. CD5, CD30, CD3, CD20 and CD45 were immunohistochemically evaluated. Plasma levels of vascular endothelial and platelet derived growth factors (VEGF, and PDGF), tumor necrosis factor (TNF-${\alpha}$), transforming growth factor (TGF-${\beta}$), interleukin-6 (IL-6), IL-8, IL-4, IL-12 and interferon gamma (IFN-${\gamma}$) were detected by enzyme-linked immunosorbent assay (ELISA). HCV+ve NHL patients showed a significant reduction in VEGF, PDGF, IFN-${\gamma}$, CD5 and CD45 and a significant increase in IL-12 and IL-8. In conclusion, there was a significant change in cytokine secretion and expression of CD markers in HCV+ve NHL patients. Based on our results, HCV infection in NHL patients requires more in-depth investigations to explore any role in lymphoma progression.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3137-3140
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• 2015

Objective: To explore the immune reconstitution of $CD4^+T$ cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of $CD4^+T$ cells were investigated. Results: The number of $CD4^+T$ cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-${beta}$ (TGF-${beta}$) was decreased (p<0.01). There was no statistically significant difference level of interferon-${\gamma}$ (IFN-${\gamma}$) (p>0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-${beta}$ and IFN-${\gamma}$ levels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of $CD4^+T$ cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

• Journal of Animal Science and Technology
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• v.55 no.2
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• pp.131-139
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• 2013

The aim of this study was to assess the effects of housing systems on physiological and immunological responses as stress indicators in laying hens. A total of 500 White Leghorn aged 16 weeks were allotted into ten conventional cages (10 birds/cage and 810 $cm^2$/bird) and four floor pens (100 birds/pen and 2,800 $cm^2$/bird) for 24 weeks. The hens housed in conventional cages with higher stocking density resulted in a significantly (P<0.05) lower BW compared with those housed in floor pens with lower stocking density without affecting the relative weights of immune organs between housing conditions. In plasma biochemical values, cholesterol and corticosterone were significantly (P<0.05) lower in the hens housed in floor pens compared with those housed in conventional cages. In pro-inflammatory cytokines, hepatic interleukin (IL)-10 and interferon-gamma (IFN-${\gamma}$) levels were significantly (P<0.05) higher in the hens housed in conventional cages compared with those kept in floor pens. Splenic and thymic IFN-${\gamma}$ expression was significantly (P<0.05) up-regulated in the hens kept in conventional cages compared with those kept in floor pens without affecting IL-1, IL-10, lipopolysaccharide- induced tumor necrosis factor-${\alpha}$ factor (LITAF) and inducible nitric oxide synthase (iNOS). In the bursa of Fabricius, IL-10 and iNOS expression of the hens housed in conventional cages were significantly (P<0.05) higher compared with those of the hens housed in floor pens. In conclusion, layers housed in conventional cages enhanced plasma cholesterol, corticosterone and some pro-inflammatory cytokines in the immune organs compared with those in floor pens.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.922-927
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• 2005

In the present study, baicalin, baicalein, and wogonin, a major flavone isolated from Scutellaria Radix were examined for their effects on PMA-induced Interlukin-6 (IL-6), $interferon-\gamma(IFN-\gamma)$, tumor necrosis factor $(TNF)-\alpha$, IL-4, IL-10, and IL-13 productions in the PMA-stimulated $CD4^+$ Jurkat T cells. These three compounds inhibited PMA-induced Th1 cytokine $(IL-6,\;IFN-\gamma,\;TNF-\alpha)$ and Th2 cytokine (IL-4 and IL-13) productions in a concentration-dependent manner. But wogonin, but not baicalin baicalein, increased PMA-induced IL-10 production. These results suggest that baicalin, baicalein, and wogonin, a major flavone modulate Th1 and Th2 cytokine productions in $CD4^+$ Jurkat T cells and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.26-36
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• 2005

Objective : Many traditional herbal remedies exhibit several beneficial effects including anti-inflammation. Euonymus alatus (Thunb.) Sieb (EA), known as Gui jun woo in Korea, has long been used in folk medicine to regulate Qi (bodily energy) and blood circulation, relieve pain, eliminate stagnant blood, and treat dysmenorrhea in oriental countries. The exact mechanism of the anti-inflammatory action of Euonymus alatus (Thunb.) Sieb (EA), however, has not been determined. Methods: Since there is increasing evidence that nitric oxide (NO) plays a crucial role in the pathogenesis of inflammatory diseases, this study was undertaken to address whether the methanol (MeOH) extract and its fractions of the bark of EA could modulate the expression of inducible NO synthase (iNOS) in thioglycollate-elicited murine peritoneal macrophages and murine macrophage cell line, RA W264.7 cells. Results: Stimulation of the peritoneal macrophages and RAW264.7 cells with $interferon-\gamma\;(IFN-\gamma)$ and lipopolysaccharide (LPS) resulted in increased production of NO in the medium. However, the butanol (BuOH) fraction of the MeOH extract of EA barks showed marked inhibition of NO synthesis in a dose-dependent manner. The inhibition of NO synthesis was reflected in the decreased amount of iNOS protein, as determined by Western blotting. The BuOH fraction did not affect the viability of RA W264.7 cells, as assessed by methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay; rather, it reduced endogenous NO-induced apoptotic cell death via inhibition of NO synthesis in RAW264.7 cells. On the other hand, the MeOH and BuOH fraction showed no inhibitory effect on the synthesis of NO by RAW264.7 cells, when iNOS was already expressed by the stimulation with $IFN-\gamma$ and LPS. Conclusion: Collectively, these results demonstrate that the MeOH and BuOH fraction inhibits NO synthesis by inhibition of the induction of iNOS in murine macrophages.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.203-208
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• 2005

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ upon stimulation by IFN-${\gamma}$/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-${\gamma}$/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and $PGE_2$ in macrophages by inhibiting iNOS and COX-2 expression.

• Journal of Haehwa Medicine
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• v.12 no.1
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• pp.1-9
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• 2003

This experimental study was carried out to evaluate the effects of Kimchi intake of Acanthopanacis cortex extract (APCE) supplementation on cytokine-induction and immune response in mice. To study in experiments using male Balb/c mice fed Kimchi and Kimchi of APCE supplementation (addition of 2% of total Kimchi weight) containing fed experimental diet during 2 weeks. Experimental mice were fed control diet or diet containing freeze-dried Kimchi at the level of 5%(w/w) or 5% freeze-dried Kimchi with 2% APCE supplementation. The main ingredient of Kimchi was Korean cabbage and fermentation was carried out at $4^{\circ}C$ for three weeks. Freeze-dried 2% APCE supplementation was added to Kimchi at the begining of fermentation. In order to investigate the effect of Kimchi intake of APCE supplementation (5%Kimchi-2%APCE), the following was performed; body weight, food intake, hematological parameter, serum level of mouse interleukin-4 (mlL-4) and mouse interferon-$\gamma$ (mIFN-$\gamma$ ), and, the percentage of CD3+/CD4+, CD3+/CD8+, B220+ in splenic cells. The results of final body weight, and food diet intake of two Kimchi groups were lower than those of the control group (not supplemented experimental diet). The hematology change obtained from the level of WBC (white blood cell) and platelet were not affected by feeding different dietary regiments, but the level of RBC (red blood cells) HB (hemoglobin), and spleen weight of two Kimchi groups were increased significantly than those of the control group. The serum level of IL-4 and IFN-$\gamma$ of two Kimchi groups were increased significantly than those of the control group, also enhanced the percentages of the CD3+/CD4+ and CD3+/CD8+ by 5% freeze-dried Kimchi, and 5%Kimchi-2%APCE group were 43.9 and 65.2%, and 96.0 and 208% than those of the control group, respectively. From these results, it can be concluded that Kimchi itself has an immuno-stimulatory effect and Kimchi contaning 2% APCE supplementation has the more pronounced effect in vivo system.

• IMMUNE NETWORK
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• v.13 no.1
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• pp.34-41
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• 2013

Interleukin-18 (IL-18) has been known to induce interferon-${\gamma}$ (IFN-${\gamma}$) production and promote Th1 immunity. Although mammalian IL-18 has been characterized in great detail, the properties and application of chicken IL-18 remain largely uninvestigated as of yet. In this study, we evaluated the immunomodulatory properties of Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 (chIL-18) on immune responses induced by avian influenza (AI) and Newcastle disease (ND) vaccines. After oral administration of S. enterica serovar Typhimurium expressing chIL-18, chickens were vaccinated intramuscularly with the recommended dose of either inactivated AI H9N2 vaccine or ND (B1 strain) vaccine. Chickens receiving a primary vaccination were boosted using the same protocol 7 days later. Humoral and cell-mediated immune responses were evaluated in terms of HI antibody titers and proliferation and mRNA expression of IFN-${\gamma}$ and IL-4 of peripheral blood mononuclear cells (PBMC) in response to specific antigen stimulation. According to our results, oral administration of S. enterica serovar Typhimurium expressing chIL-18 induced enhanced humoral and Th1-biased cell-mediated immunity against AI and ND vaccines, compared to that of chickens received S. enterica serovar Typhimurium harboring empty vector. Therefore, we conclude that our proposed vaccination regimen using inactivated AI and ND viruses along with oral administration of S. enterica serovar Typhimurium expressing chIL-18 may provide a novel approach in protecting chicken from currently circulating AI and ND virus strains.