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The Effect of Allergic Inflamation by Sophora Flavescens Aiton Extract Ion Through Inhibition of the $NF{\kappa}B$, JNK and p38 Pathway (고삼(苦蔘)에탄올 추출물이 $NF{\kappa}B$ 및 JNK, p38 조절을 통한 알레르기성 염증에 미치는 영향)

  • Lee, Ji-Young;Park, Seong-Sik
    • Journal of Sasang Constitutional Medicine
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    • v.21 no.1
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    • pp.139-149
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    • 2009
  • 1. Objectives The roots of Sophora flavescens Aiton (SFA) are widely used as a herbal remedy for allergic inflammation. In this study, we invested the effect of SFA on passive cutaneous anaphylaxis reaction and histamin releas and we demonstrated that SFA suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin- 6 (IL-6), and interleukin -8 (IL-8), through inhibition of the $NF{\kappa}B$, JNK and p38 pathway in the human mast cell line, HMC-1. 2. Methods To accomplish this, we invested passive cutaneous anaphylaxis reaction and histamin release at an animal experiment. In addition, we investigated the effect of SFA on the production of inflammation-related cytokines in HMC-1 cells that were co-treated with PMA and A23187, which can induce production of pro-inflammatory cytokines. 3. Results and Conclusions SFA induced passive cutaneous anaphylaxis reaction and histamin releas and supressed the expression of TNF-${\alpha}$, IL-6, and IL-8. In addition, the protein levels of TNF-${\alpha}$ were also decreased by SFA treatment. Furthermore, SFA inhibited the nuclear translocation of nuclear factor $NF{\kappa}B$ through inhibition of the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which is an inhibitor of $NF{\kappa}B$. Moreover, SFA also inhibited induction of MAPKs (JNK, p38) and $NF{\kappa}B$ promoter-mediated luciferase activity. Taken together, these results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

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Effect of Foeniculum Vulgare extract on inflammatory response in lipopolysaccharide exposed rats (회향(茴香) 추출물이 LPS를 처리한 Rat의 염증반응에 미치는 영향)

  • Heo, Seong-Kyu;Lee, Eun;Park, Won-Hyung;Cha, Yoon-Yop
    • Journal of Korean Medicine Rehabilitation
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    • v.23 no.2
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    • pp.73-83
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    • 2013
  • Objectives : This study was performed to investigate the effects of Foeniculum Vulgare(FV) extract on the anti-inflammatory of lipopolysaccharide(LPS) exposed rats. Methods : We divided LPS exposed Sprague-Dawley rats into 4 groups. They were control group, feed with 100 mg/kg, 200 mg/kg, 300 mg/kg FV groups. They were administered for 6 weeks. We measured the concentration of plasma interleukin-1${\beta}$(IL-1${\beta}$), plasma interleukin-6(IL-6), plasma tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), plasma interleukin-10(IL-10), the concentration of liver IL-1${\beta}$, IL-6, TNF-${\alpha}$ and IL-10. Results : 1. Plasma IL-1${\beta}$, plasma IL-6 and plasma TNF-${\alpha}$ concentration increased rapidly at 2hours after LPS injection and maintained high levels at 5hours after LPS injection. The concentration of these cytokines in the FV extract groups showed lower values than control group(P<0.05). 2. The concentration of Plasma IL-10 in FV extract groups showed higher values than control group at all times(P<0.05). 3. The concentration of liver IL-1${\beta}$ and IL-6 in FV extract groups showed lower values than control group(P<0.05). The concentration of liver TNF-${\alpha}$ in FV extract groups showed a tendency to decrease and that of liver IL-10 in FV extract groups showed a tendency to increase; however, these values showed no significantly different. Conclusions : In inflammatory response by LPS derivation, the FV gives positive effect.

Anti-inflammatory Effects of Allium victorialis Extract in Lipopolysaccharide Exposed Rats and Raw 264.7 Cells

  • Lee, Eun
    • Korean Journal of Plant Resources
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    • v.27 no.6
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    • pp.707-713
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    • 2014
  • This study examined the inflammatory reaction effects of Allium victorialis var. platyphyllum in vivo at the time of a lipopolysaccharide (LPS) shock in rats, and in vitro in cultured Raw 264.7 cells, with the aim of facilitating the development of a new anti-inflammatory medicine. Plasma concentrations of interleukin (IL)-$1{\beta}$, IL-6, tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$), and IL-10 in rats peaked 5 h after LPS treatment in all experimental groups, with those of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ being significantly lower in all animals treated with A. victorialis than in the control group at that time point. Conversely, the plasma concentration of IL-10 was higher in the rats treated with 300 mg/kg A. victorialis extract than in the control group at both 2 and 5 h after LPS treatment. Concentrations of IL-$1{\beta}$ and IL-6 in the liver of rats treated with A. victorialis extract were significantly lower than those of the saline-treated control group. However, the liver concentrations of TNF-${\alpha}$ and IL-10 did not vary significantly between the four animal groups. Similarly, concentrations of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ obtained from cultured Raw 264.7 macrophages were lower in all of the A.-victorialis-extract-treated groups than in the control group. Although the concentration of IL-10 in the A.-victorialis-extract-treated groups tended to be greater than in the control group, the differences between groups were not statistically significant. Together the findings of this study suggest that A. victorialis var. platyphyllum contains functional substances that are involved in inflammatory reactions.

Effect of Asterina pectinifera Lectin on Cytokine Production (별불가사리(Asterina pectinifera) 렉틴의 사이토카인 생성 양상)

  • 전경희;최수정;정시련
    • YAKHAK HOEJI
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    • v.43 no.4
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    • pp.474-480
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    • 1999
  • The purpose of this study is to define whether Asterina pectinifera Lectin (APL) is effective on the cytokine production. Isolated mRNA from hPBMC (human peripheral blood mononuclear cells) stimulated with APL for various reaction times (1 to 96 hours) was detected by RT-PCR. The intensity of band for IL-1 and $IFN{\gamma}$ mRNA was markedly increased at l hour, and IL-2 mRNA was strongly expressed at 4 hours. The mRNA band of APL-induced IL-2 and $IFN{\gamma}$ was weaker than that of IL-1, IL-6 and $TNF{\alpha}$. The mRNA expression of 4 cytokines (IL-1, IL-2, $IFN{\gamma}$ and $TNF{\alpha}$) was detected up to 48 hours, and that of IL-6 was detected until 72 hours. ELISA was used to look protein secretion of the cytokine gene with IL-1, IL-2 and TNF$\alpha$expressed strongly in RT-PCR. The highest protein secretion was at 4 hours with IL-1, at 8 hours with IL-2 and at 4 hours with $TNF{\alpha}$. These results suggest that APL can induce the production of some cytokines and the immune response from PBMC was done within the first few hours of stimulation with APL.

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Cytokine Induction of Intercellular Adhesion Molecule-1(ICAM-1) Expression on Human Glioblastoma Cell Line, U-251 MG, U-373 MG (교모세포종 U-251MG, U-373MG세포주의 Cytokines처리에 의한 세포내 ICAM-1 발현)

  • Lee, Jong-Won;Kwon, Jung-Taek;Min, Byung-Kook;Park, Seung-Won;Kim, Young-Baeg;Hwang, Sung-Nam;Suk, Jong-Sik;Choi, Duck-Young
    • Journal of Korean Neurosurgical Society
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    • v.29 no.4
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    • pp.477-484
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    • 2000
  • Objective : Despite advances in the understanding of tumor biology and the tumor immunology, there has been no effective treatment. The Intercellular adhesion molecule-1(ICAM-1) has been shown to be important in interaction involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon($IFN-{\gamma}$) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$). ICAM-1 has been identified as one of the ligands for lymphocyte function-associated antigen-1(LFA-1). The effectiveness of various cytokines to ICAM-1 induction on cultured human glioblastoma cell lines and potential efficacy of immunotherapy were studied. Method : Human glioblastoma cell lines, U-251 MG, U-373 MG were trypsinized and suspended at $1{\times}10^5cells/ml$ and grown on 8 well chamber slide, the cells were incubated in 0.3ml medium alone or medium containing $IFN-{\gamma}$(1000U/ml) or $TNF-{\alpha}$(250U/ml) or $IFN-{\gamma}$ plus $TNF-{\alpha}$ for 6, 12, 24, 48 and 72 hours. The coverslip were then removed and stained with a 1/30 dilution of anti-ICAM-1 antibody. Result : Surface antigen expression of ICAM-1 was increased by incubating glioblastoma cell lines with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\gamma}$ and $TNF-{\alpha}$ has induced more ICAM-1 expression on glioblastoma cell lines. Upregulation of ICAM-1 expression in an established glioblastoma cell line was of greater magnitude and more rapid following incubation with $IFN-{\gamma}$ plus $TNF-{\alpha}$. Surface antigen expression of ICAM-1 was increased for up to 48 hours after cytokine treatment on both cell lines(p<0.05). There was no difference on both cell lines(p>0.05). Conclusion : The results of the present study indicate that ICAM-1 expression in glioblastoma cell lines, U-251 MG and U-373 MG, are induced and enhanced after treatment with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\alpha}$ and $TNF-{\gamma}$ is stronger and more rapid than $IFN-{\gamma}$ or $TNF-{\alpha}$ alone.

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Effect of Ginsenosides from Panax Ginseng on TNF-${\alpha}$ Production and T Cell Proliferation (인삼 사포닌류가 종양괴사인자의 생성 및 T 세포 증식에 미치는 효과)

  • Cho, Jae-Youl;Park, Ji-Soo;Yoo, Eun-Sook;Baik, Kyong-Up;Park, Myung-Hwan;Han, Byung-Hoon
    • YAKHAK HOEJI
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    • v.42 no.3
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    • pp.296-301
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    • 1998
  • To investigate the effects of ginsenosides from Panax ginseng on mitogenic responses in macrophages and splenocytes from murine, we examined the effects of representative protopanaxadiol and protopanaxatriol ginsenosides ($Rb_1,\;Rb_2,\;Re\;and\;Rg_1$) on tumor necrosis factor-${\alpha}$ (TNF-(${\alpha}$) production in murine macrophage cell line (RAW264.7 cells) stimulated by lipopolysaccharide (LPS) and T cell proliferation in splenocytes stimulated by concanavalin A (Con A). Among the ginsenosides tested, protopanaxadiol ginsenosides ($Rb_1\;and\;Rb_2$) significantly inhibited TNF-${\alpha}$ production in a dose-dependent manner. However, protoppanaxatriol ginsenosides (Re and $Rg_1$) showed little inhibitory activity. The molar concentrations of $Rb_1\;and\;Rb_2$ producing 50% inhibition ($IC_{50}$) of TNF-${\alpha}$ production were $55.8{\mu}g/ml\;(48.0{\mu}M)\;and\;31.8{\mu}g/ml (27.9{\mu}M)$, respectively. As a positive control, prednisolone also exhibited inhibitory activity with an $IC_{50}$ value of $21.7{\mu}M$. In T cell proliferation, $Rg_1$, was not effective but $Rb_1$ and Re or $Rb_2$ significantly increased or inhibited at high concentration, 75 and $100{\mu}g/ml$. In contrast, prednisolone showed potent inhibitory activity with an $IC_{50}$ value of 6.1nM. These results suggest that ginsenosides may take part in the mitogen-induced signaling pathway for TNF-${\alpha}$ production and T cell proliferation from macrophages and splenocytes.

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Effects of Ethyl Pyruvate on Allodynia, TNF-${\alpha}$ Expression, and Apoptosis in the Dorsal Root Ganglion after Spinal Nerve Ligation Injury

  • Choi, Dae-Kee;Leem, Jeong-Gill;Shin, Jin-Woo;Suh, Jeong-Hun
    • The Korean Journal of Pain
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    • v.25 no.4
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    • pp.213-220
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    • 2012
  • Background: It has been demonstrated that the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and apoptotic cell death in the dorsal root ganglion (DRG) following spinal nerve constriction injury play a role in the initiation and continuation of hyperalgesia and allodynia. The present study was designed to investigate the effects of ethyl pyruvate (EP) on mechanical and cold allodynia, TNF-${\alpha}$ expression, and apoptosis in DRG after spinal nerve ligation injury. Methods: Rats were divided into 3 groups: control, pre-EP, and post-EP. EP (50 mg/kg) was intraperitoneally injected 30 minutes before (pre-EP) or after (post-EP) surgery. Behavioral tests to determine mechanical and cold allodynia were conducted before surgery and 4 and 7 days after surgery. Seven days after surgery, TNF-${\alpha}$ protein levels in DRG were evaluated by enzyme-linked immunosorbent assay, and DRG apoptosis was determined by immunohistochemical detection of activated caspase-3. Results: Treatment with EP significantly reduced mechanical and cold allodynia following spinal nerve ligation injury. TNF-${\alpha}$ protein levels in the pre-EP ($4.7{\pm}1.2$ pg/200 ${\mu}g$; P < 0.001) and post-EP ($6.4{\pm}1.8$ pg/200 ${\mu}g$; P < 0.001) groups were 2-3 times lower than the control group ($14.4{\pm}1.2$ pg/200 ${\mu}g$). The percentages of neurons and satellite cells that co-localized with caspase-3 were also significantly lower in the pre-EP and post-EP groups than the control group. Conclusions: These results demonstrate that EP has a strong anti-allodynic effect that acts through the inhibition of TNF-${\alpha}$ expression and apoptosis in DRG after spinal nerve ligation injury.

Dynamic Patterns of Systemic Innate Immunity and Inflammatory Associated Factors in Experimental Caprine Coccidiosis

  • Tadayon, Shabnam;Razavi, Seyed Mostafa;Nazifi, Saeed
    • Parasites, Hosts and Diseases
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    • v.54 no.6
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    • pp.719-724
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    • 2016
  • The present study was designed to assess the dynamic patterns of pro-inflammatory cytokines, including $IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6, acute phase protein (${\alpha}1$-acid-glycoprotein, AGP), and an inflammation associated factor (adenosine deaminase; ADA) following experimental caprine coccidiosis. Ten kids aging from 2 to 4 months were infected orally with $5{\times}10^4$ sporulated oocysts and 10 animals served as controls. Blood samples were collected in both groups before infection and at days 3, 7, 14, 21, 28, and 35 post-infection (PI), and the levels of above-mentioned factors were measured. $IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6, AGP, and ADA activities were significantly higher in infected animals from day 7 PI (P<0.05). In conclusion, the circulatory levels of most systemic inflammatory markers, including pro-inflammatory cytokines ($IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6), AGP, and ADA increased significantly starting from day 3 to day 7 PI in caprine coccidiosis.

Selection of Flavonoids Inhibiting Expression of Cell Adhesion Molecules Induced by Tumor Necrosis Factor- a in Human Vascular Endothelial Cells (종양괴사인자에 의하여 유도된 혈관내피세포의 Cell Adhesion Molecules 발현을 억제시키는 플라보노이드 선별)

  • 최정숙;최연정;박성희;이용진;강영희
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.6
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    • pp.1134-1141
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    • 2002
  • Adhesion of leukocytes to the activated vascular endothelium and their subsequent recruitment/migration into the artery wall are key features in the pathogenesis of atherosclerosis and inflammatory diseases. These features have been mediated by cell adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) and in tracellular cell adhesion molecule-1 (ICAM-1). This study examined whether flavonoids inhibit the pro-inflammatory cytokine TNF-$\alpha$-induced monocyte adhesion via a modulation of the protein expression of VCAM-1 and ICAM-1 of human umbilical vein endothelial cells (HUVECs). TNF-$\alpha$ markedly increased the adhesion of THP-1 monocytes to endothelial cells and induced the expression of VCAM-1, ICAM-1 and E-selectin proteins in HUVECs. Micromolar concentrations of the flavones luteolin and apigenin and the flavonol quercetin near completely blocked the monocyte adhesion to the activated endothelial cells and the induction of these adhesion molecules. However, equimicromolar catechins of (-)epigallocatechin gallate and (+)catechin, the flavonol myr- icetin and the flavanones of naringin and hesperidin had no effect on TNF-$\alpha$-activated monocyte adhesion. (-)Epigallocatechin gallate, (+) catechin, and naringin did not attenuate the TNF-$\alpha$ induction of these adhesion molecules. Furthermore, culture with luteolin and apigenin strongly blocked the expression of TNF-$\alpha$-induced VCAM-1 mRNA and modestly attenuated ICAM-1 mRNA. Quercetin modestly decreased the TNF-$\alpha$-activated VCAM-1 and ICAM-1 mRNAs. These results demonstrate that flavonoids classified as flavones and flavonols may inhibit monocyte adhesion to the TNF-$\alpha$-activated endothelium, most likely due to a blockade of expression of functional adhesion molecules down-regulated at the transcriptional level, indicating a definite linkage between the chemical structure of flavonoids and the expression of cell adhesion molecules. Furthermore, the antiathero-genic feature of flavonoids appears to be independent of their antioxidant activity.

Effect of Lactic Acid Bacteria (Lactobacillus acidophilus, Streptococcus thermophilus, Bsfidobacterium bifidum) on the Enhancement of the Production of Nitric Oxide and TNF-$\alpha$ in RAW 264.7 Macrophage Cell (RAW 264.7 대식세포에서의 유산균에 의한 Nitric Oxide와 $TNF-{\alpha}$의 생성 증가 효과)

  • Park So Hee;Chung Myung Jun;Kim Soo Dong;Baek Dae Heoun;Kang Byoung Yong;Ha Nam Joo
    • YAKHAK HOEJI
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    • v.49 no.6
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    • pp.459-464
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    • 2005
  • The immune reinforcement of the probiotic lactic acid bacteria Lactobacillus acidophilus, Streptococcus thermophilus and Bifidobacterium bifidum was studied in RAW 264.7 cell line treated with diluted solution (dilution to $2^{5}$) of the supernatnats of lactic acid bacteria. RAW 264.7 cell line was used as a macrophage model to assess the effects of lactic acid bacteria on the production of nitric oxide (NO) and cytokine tumor necrosis factor (TNF)-$\alpha$ and cell morphological changes. The production of NO and TNF-$\alpha$ were largely affected by lactic acid bacteria in dose-dependent manner in 24 or 48 hr cultures and cell morphological changes were also largely affected by lactic acid bacteria. Especially Bifidobacterium bifidum differentially stimulated the production of NO and TNF-$\alpha$. NO production was increased by Bifidobacterium bifidum 25 $\mu$l/ml more than LPS (20 ng/ml) control, and TW-$\alpha$ by Bifidobacterium bifidum 6.25 $\mu$l/ml more than LPS (10 ng/ml) control. The in vitro approaches employed here should be useful in further characterization of the effects of lactic acid bacteria on systemic immunity.