• Title/Summary/Keyword: Interferon alpha

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Acacia ferruginea Inhibits Tumor Progression by Regulating Inflammatory Mediators-(TNF-α, iNOS, COX-2, IL-1β, IL-6, IFN-γ, IL-2, GM-CSF) and Pro-Angiogenic Growth Factor-VEGF

  • Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekaran
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3909-3919
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    • 2013
  • The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$) in animals with DLA induced solid tumours. Increase in $CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

Efficient Induction of Th1-type Immune Responses to Hepatitis B Virus Antigens by DNA Prime-Adenovirus Boost

  • Lee, Chang-Geun;Yang, Se-Hwan;Park, Su-Hyung;Song, Man-Ki;Choi, So-Young;Sung, Young-Chul
    • IMMUNE NETWORK
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    • v.5 no.1
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    • pp.1-10
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    • 2005
  • Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

T Cell Immunoglobulin Mucin Domain (TIM)-3 Promoter Activity in a Human Mast Cell Line

  • Kim, Jung Sik;Shin, Dong-Chul;Woo, Min-Yeong;Kwon, Myung-Hee;Kim, Kyongmin;Park, Sun
    • IMMUNE NETWORK
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    • v.12 no.5
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    • pp.207-212
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    • 2012
  • T cell immunoglobulin mucin domain (TIM)-3 is an immunomodulatory molecule and upregulated in T cells by several cytokines. TIM-3 also influences mast cell function but its transcriptional regulation in mast cells has not been clarified. Therefore, we examined the transcript level and the promoter activity of TIM-3 in mast cells. The TIM-3 transcript level was assessed by real-time RT-PCR and promoter activity by luciferase reporter assay. TIM-3 mRNA levels were increased in HMC-1, a human mast cell line by TGF-${\beta}1$ stimulation but not by stimulation with interferon (IFN)-${\alpha}$, IFN-${\lambda}$, TNF-${\alpha}$, or IL-10. TIM-3 promoter -349~+144 bp region relative to the transcription start site was crucial for the basal and TGF-${\beta}1$-induced TIM-3 promoter activities in HMC-1 cells. TIM-3 promoter activity was increased by over-expression of Smad2 and Smad4, downstream molecules of TGF-${\beta}1$ signaling. Our results localize TIM-3 promoter activity to the region spanning -349 to +144 bp in resting and TGF-${\beta}1$ stimulated mast cells.

The Effect of Magnolia Bark on the Metabolic Inflammation and Insulin Resistance of ob/ob Mice (후박(厚朴)이 ob/ob 마우스의 대사성 염증과 인슐린 저항성에 미치는 영향 및 관련기전에 대한 연구)

  • Kim, Hyo-jae;Kim, Eun-ji;Ma, Young-hoon;Han, Yang-hee
    • The Journal of Internal Korean Medicine
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    • v.39 no.4
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    • pp.751-763
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    • 2018
  • Objective: This study was undertaken to investigate how magnolia bark extract affects ob/ob mouse in terms of metabolic inflammation and insulin resistance. Methods: Leptin-deficient ob/ob mice were divided into 2 groups (n=5): a normal saline treatment (=control) and magnolia bark treatment. Wild type mice were the lean group (n=5). After 5 weeks, we measured fasting blood sugar (FBS) and conducted oral glucose tolerance tests (OGTTs) in each group. After 6 weeks, we measured body weight, epididymal fat pad weight, liver weight, serum glucose, serum insulin, and gene expression of tumor necrosis factor-${\alpha}$, interferon-${\gamma}$, and interleukin-6. We characterized the phenotype of adipose tissue macrophages (ATMs) and analyzed fractions of the phenotype in each group by flow cytometry. Results: In the magnolia bark group, fasting blood sugar, oral glucose tolerance levels, and insulin resistance (HOMA-IR) were significantly decreased. The population and proportion of ATMs among leukocytes in adipose tissue were significantly decreased in the magnolia bark group. The population and proportion of M1 type ATMs among ATMs were significantly decreased in the magnolia bark group. Gene expression of tumor necrosis factor-${\alpha}$ was significantly decreased in the magnolia bark group. Conclusions: These results support a positive effect of magnolia bark on metabolic diseases such as insulin resistance and metabolic inflammation in leptin-deficient ob/ob mice.

Anticancer and Related Immunomodulatory and Anticachexic Effects of Insamyangyoung-tang Extracts on Non Small Cell Lung Carcinoma, NCI-H520, Xenograft Mice (인삼양영탕(人蔘養榮湯)이 비소세포 폐암세포 이식 마우스에서 항암, 면역활성 및 악액질 억제에 미치는 영향)

  • Song, Kwang Kyu;Park, Mee Yeon;Choi, Hae Yun;Kim, Jong Dae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.1
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    • pp.63-77
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    • 2013
  • The object of this study was to observe anticancer and related immunomodulatory and anticachexic effects of Insamyangyoung-tang aqueous extracts (ISYYTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Changes on the tumor volume and weights, lymphatic organ(spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes and peritoneal macrophage activities (NK cell activity), splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents, splenic T-lymphocyte subsets (CD3+, CD4+ and CD8+) and TNF-${\alpha}+$ cells were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. In addition, changes on the body weights, epididymal fat weights and serum IL-6 levels were also detected with the thicknesses of deposited cervical brown adipose tissue and their mean diameters to monitor the tumor-related anticachexic effects. The results obtained in this study suggest that over 50 mg/kg of ISYYTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory and anticachexic effects. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.

Effect of Ethanol on Prostaglandins Production of Monocytes (에탄올이 단핵구의 Prostaglandins 생산에 미치는 영향)

  • 박란숙
    • Journal of Nutrition and Health
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    • v.24 no.2
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    • pp.97-103
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    • 1991
  • The increase in alcohol consumption level has been noticed in Korea recently. Alcohol appreciably inhibits cell mediated immunity and this may contribute to the high prevalence of serious infection such as pulmonary tuberculosis among alcoholic subjects. The present study was undertaken to examine the effect of ethanol on the cyclooxygenase metabolites of human monocyte in vitro. Monocytes were activated with 800 units of gamma interferon(IFN-${\gamma}$) for 3 days following apply of Ficool-hypaque density gradient and gelatin coated flasks for separation of monocytes. Ethanol with addition of 100mM, 300mM and 600 mM for 30 minutes to 106 monocytes with/without previous IFN-${\gamma}$ treatment caused a dose dependent decrease in the production of thromboxane B2, 6-keto-PGE1$\alpha$ and PGE2 by radioimmunoassay at 6 hours after ethanol treatment. Quite different from the findings after 6 hours there was dose dependent increase in three prostaglandins without IFN-${\gamma}$ treatment after 24 hours of incubation. With previous treatment of IFN-${\gamma}$ reduced productions of three prostaglandins at 24 hours than control is spite of ethanol stimjulation. These findings show that IFN-${\gamma}$ can inhibit alcohol induced derangement of arachidonic acid metabolism of monocytes.

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The Modulating Effect of β-1, 3/1, 6-glucan Supplementation in the Diet on Performance and Immunological Responses of Broiler Chickens

  • Zhang, Bo;Guo, Yuming;Wang, Zhong
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.2
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    • pp.237-244
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    • 2008
  • The object of this trial was to investigate the effect of dietary ${\beta}$-1,3/1,6-glucan supplementation on the performance and immunological response of broiler chickens. Two hundred and forty 1-day old male broilers ($39{\pm}1g$) were separated into six treatments which were given six different feeds containing 0 (control), 25, 50, 75, 100 and 125 mg/kg dietary ${\beta}$-1,3/1,6-glucan supplementation. On days 21 and 42, body weight gain, feed consumption and feed conversation rate were recorded as measures of growth performance. The levels of key cytokines in the immuno-regulating pathway: interleukin-1 (IL-1), interleukin-2 (IL-2), interferon $\gamma$(IFN-$\gamma$, tumor necrosis factor $\alpha$(TNF-$\alpha$, and the concentrations of signal molecules: peripheral blood plasma globulin, serum Immunoglobulin G (IgG) and intestinal secretary Immunoglobulin A (sIgA), were measured as indices of the immune response to determine suitable levels of dietary ${\beta}$-1,3/1,6-glucan supplementation. The results indicated that performance was elevated quadratically with dietary ${\beta}$-1,3/1,6-glucan supplementation. Maximal growth performance and an enhanced immunological response were obtained at a supplemented level of 50 mg/kg.

The Protective Role of TLR3 and TLR9 Ligands in Human Pharyngeal Epithelial Cells Infected with Influenza A Virus

  • Han, Yan;Bo, Zhi-Jian;Xu, Ming-Yu;Sun, Nan;Liu, Dan-Hong
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.3
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    • pp.225-231
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    • 2014
  • In this study we aim to extensively investigate the anti-influenza virus immune responses in human pharyngeal epithelial cell line (Hep-2) and evaluate the protective role of Toll-like receptor (TLR) ligands in seasonal influenza A H1N1 (sH1N1) infections in vitro. We first investigated the expression of the TLRs and cytokines genes in resting and sH1N1 infected Hep-2 cells. Clear expressions of TLR3, TLR9, interleukin (IL)-6, tumour necrosis factor (TNF)-${\alpha}$ and interferon (IFN)-${\beta}$ were detected in resting Hep-2 cells. After sH1N1 infection, a ten-fold of TLR3 and TLR9 were elicited. Concomitant with the TLRs activation, transcriptional expression of IL-6, TNF-${\alpha}$ and IFN-${\beta}$ were significantly induced in sH1N1-infected cells. Pre-treatment of cells with poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) resulted in a strong reduction of viral and cytokines mRNA expression. The results presented indicated the innate immune response activation in Hep-2 cells and affirm the antiviral role of Poly I:C and CpG-ODN in the protection against seasonal influenza A viruses.

Inhibitory effects of Cervi Pantotrichum Cornu herbal acupuncture on type II collagen-induced arthritis (Type II Collagen으로 유발된 관절염에 대한 녹용약침의 억제효과에 관한 연구)

  • Kim, Jin-gyu;Kim, Kap-sung
    • Journal of Acupuncture Research
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    • v.19 no.6
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    • pp.155-170
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    • 2002
  • 면역억제와 면역항진의 작용을 지닌 녹용(鹿茸)약침의 실험쥐에서의 type II collagen(CII)으로 유발된 관절염(CIA)에 대한 효과를 연구하였다. 본 실험에서 녹용(鹿茸)약침군과 생리식염수군을 대조군으로 하여 실험쥐에게 약침시술을 하였다. 녹용(鹿茸)약침이 CII에 작용하는 세포반응에 대한 효과를 검정하였는데, 대조군에서는 CII 유발주사 후 24일에 관절염이 관찰되었고, CIA의 정도가 점차적으로 심해졌다. 생리식염수 처리군과 비교해 24일 동안 하루에 한번 $50{\mu}g/kg$ 이상 용량의 녹용(鹿茸)약침은 CII 처리 T cell의 interleukin 2(IL-2)와 interferon-${\gamma}$($IFN-{\gamma}$) 생산능력을 억제했다. 또한 녹용(鹿茸)약침은 CII처리 임파절과 대식세포의 tumor necrosis facter ${\alpha}$($TNF-{\alpha}$)의 생산을 억제했다. 한편 CIA에 대한 약침효능의 지표는 녹용(鹿茸)약침을 14일간 하루에 한번씩 처리하면서, 소의 CII로 3주 간격으로 2번 유발접종을 실시하여 검정하였다. 첫 CII 유발접종과 동시에 일일 투여량 $100{\mu}g/kg$으로 14일간의 녹용(鹿茸)약침이 항체형성과 CII에 대한 지연형 과민성 뿐만 아니라 관절염의 증가도 막아주었다. 녹용(鹿茸)약침을 관절염 유발성 CII의 2차 접종과 동시에 시술한 결과, 관절염과 CII에 대한 면역반응을 억제하였다. 이에 저자는 CII로 유발된 관절염에 대한 녹용(鹿茸)약침의 억제효과에 대하여 보고하는 바이다.

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Effects of Topical application of Astragalus membranaceus in Spontaneous Alopecia Mice Model (황기(黃芪) 추출물의 외용 도포가 자발성 원형탈모 생쥐에 미치는 영향)

  • Kwon, Hyeok Je;Kim, Mi Hye;Yang, Woong Mo
    • The Journal of Korean Medicine
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    • v.39 no.1
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    • pp.1-12
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    • 2018
  • Objectives: Astragalus membranaceus has been reported to inhibit immune responses, but its effect on hair loss is not clear. In this study, the effect of A. membranaceus extract (AM) on hair regrowth in C57BL/6 mice with natural hair loss in the telogen phase was investigated. Methods: Mice with natural hair loss were topically treated with 1% AM on the dorsal skin for 2 weeks. Dorsal skin samples were stained with hematoxylin and eosin and probed with an anti-mouse CD8a IgG. The mRNA expression levels of tumor necrosis factor $(TNF)-{\alpha}$, interferon $(IFN)-{\gamma}$ and interleukin (IL)-4 were measured by reverse transcription polymerase chain reaction and quantitative real-time polymerase chain reaction. Results: AM treatment induced hair regrowth in hair loss mice, while control mice suffered continued hair loss. Tapering hair shafts and broken hair follicles were decreased as well as CD8+ T lymphocyte infiltration. In addition, the expressions of $TNF-{\alpha}$, $IFN-{\gamma}$ and IL-4 were reduced by AM treatment. Also, AM treatment significantly increased the KGF expressions in Hs68 fibroblast cells. Conclusion: These results suggest that topical application of A. membranaceus may be an alternative therapy for hair loss.