• Title/Summary/Keyword: $Interferon-\gamma$

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Clinical Significance of Interferon $\gamma$ Release Assay for Diagnosis of Tuberculosis in Children (소아 결핵 진단에 있어서 결핵 특이항원자극 인터페론 감마 측정검사의 임상적 의의)

  • Lee, Hee Woo;Park, Hwa Young;Ahn, Young Min;Sohn, Keun Chan
    • Pediatric Infection and Vaccine
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    • v.17 no.2
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    • pp.137-147
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    • 2010
  • Purpose : The purpose of this study is to evaluate the usefulness and limitation of QuantiFERON-TB Gold (QTB) for diagnosis of latent tuberculosis in children. Methods : The medical records of 112 children who were tested by tuberculin skin test (TST) and QTB for detection of latent tuberculosis (TB) in Eulji General Hospital during the period from January 2007 to June 2009 were retrospectively reviewed. Results : Of the 112 participants, the clinical TB group included 15 (13.4%), the contact group included 43 (38.4%), and the non-contact group included 54 (48.2%). Positive rates of TST and QTB were 100% and 80% in the clinical TB group, 64% and 14% in the close contact group, 27% and 0% in the casual contact group, and 52% and 2% in the non-contact group, respectively. Sensitivity of QTB was 80.0% and specificity was 92.6%. Agreement between QTB and TST was poor ($\kappa$=0.209). We also confirmed that the positive rate of QTB increased as the age of the patient increased (P=0.011). A QTB indeterminate result was observed in 11 (9.8%) subjects. QTB was retested in 15 subjects. In 5 of the 6 subjects who had positive results initially, positive results persisted for a median 2.2 months after termination of treatment. Conclusion : Although QTB was associated with several problems, including low sensitivity and a high rate of indeterminate results, it had clinical importance due to its high specificity. We found good correlation with regard to exposure and QTB positivity, including that of young children under 5 years of age. However, clinical application of interferon-$\gamma$ releasing assay for young children for diagnosis of active and latent tuberculosis will require additional prospective studies.

Blockade of Retinol Metabolism Protects T Cell-Induced Hepatitis by Increasing Migration of Regulatory T Cells

  • Lee, Young-Sun;Yi, Hyon-Seung;Suh, Yang-Gun;Byun, Jin-Seok;Eun, Hyuk Soo;Kim, So Yeon;Seo, Wonhyo;Jeong, Jong-Min;Choi, Won-Mook;Kim, Myung-Ho;Kim, Ji Hoon;Park, Keun-Gyu;Jeong, Won-Il
    • Molecules and Cells
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    • v.38 no.11
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    • pp.998-1006
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    • 2015
  • Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. Con A was injected into wild type (WT), Raldh1 knockout ($Raldh1^{-/-}$), $CCL2^{-/-}$ and $CCR2^{-/-}$ mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con A-mediated hepatitis by decreasing interferon-${\gamma}$ in T cells. Moreover, interferon-${\gamma}$ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL-6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore, inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con A-induced hepatitis. These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis.

Performance comparison and evaluation of interferon-gamma assay kit for bovine tuberculosis diagnosis (소 결핵 진단을 위한 인터페론감마 검사 키트의 성능 비교 평가)

  • Hong, Leegon;Choi, Woojae;Ro, Younghye;Ahn, Sunmin;Kim, Eunkyung;Choe, Eunhee;Kim, Danil
    • Korean Journal of Veterinary Service
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    • v.43 no.4
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    • pp.201-209
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    • 2020
  • In Korea, bovine tuberculosis (bTB) is a representative zoonotic disease that causes considerable economic loss. In determining the positive bTB, the ELISA method for examining the amount of interferon-gamma (IFN-γ) is included in Korea's diagnostic standard method. Recently, commercially available BIONOTE TB-Feron ELISA Plus (TB-Feron Plus) that detects IFN-γ has been introduced. However, since the scientific basis for the performance is limited, we evaluated performance by comparing it with the results of another IFN-γ ELISA assay kit (BOVIGAM®) certified by Office International des Epizooties. In our research, 42 positive blood samples preliminarily tested with a tuberculin skin test and/or BOVIGAM® and 54 negative blood samples collected from three bTB free farms were subjected to IFN-γ assay using the TB-Feron Plus and the BOVIGAM®, respectively. The result shows that the sensitivity, specificity and accuracy were 81.0% (34/42), 100% (54/54), 91.7% (88/96) in TB-Feron Plus kit and 78.6% (33/42), 100% (54/54), 90.6% (87/96) in BOVIGAM® kit, respectively. Moreover, the overall accordance percentage of the two kits was 99.0% (95/96) and there was almost perfect agreement between two assays (Kappa=0.977, P<0.0001). Furthermore, additional studies confirmed that elevated lymphocyte numbers in blood did not interfere with the results of the TB-Feron Plus kit. And, delayed time from sampling to culture decreased the optical density (OD) value. Therefore, we concluded that the TB-Feron Plus kit was not inferior to BOVIGAM® in performance. High lymphocyte numbers in blood did not impact on TB-Feron Plus results, while delayed time before culture interfered with OD value.

T cell phenotype and intracellular $IFN-{\gamma}$ production in peritoneal exudate cells and gut intraepithelial lymphocytes during acute Toxoplasma gondii infection in mice

  • Lee, Young-Ha;Shin, Dae-Whan
    • Parasites, Hosts and Diseases
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    • v.40 no.3
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    • pp.119-129
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    • 2002
  • Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

The expressions of inflammatory factors and tissue inhibitor of matrix metalloproteinase-2 in human chronic periodontitis with type 2 diabetes mellitus

  • Shin, Dong-Seok;Park, Jin-Woo;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.40 no.1
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    • pp.33-38
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    • 2010
  • Purpose: The purpose of this study was to observe and quantify the expression of interleukin-4 (IL-4), interferon-$\gamma$ (IFN-$\gamma$), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the gingival tissue of patients with type 2 diabetes mellitus (DM) and healthy adults with chronic periodontitis. Methods: Twelve patients with type 2 DM and chronic periodontitis (Group 3), twelve patients with chronic periodontitis (Group 2), and twelve healthy individuals (Group 1) were included in the study. Clinical criteria of gingival (sulcus bleeding index value, probing depths) and radiographic evidences of bone resorption were divided into three groups. The concentrations of cytokines were determined by a western blot analysis and compared using one-way ANOVA followed by Tukey's test. Results: The expression levels of IFN-$\gamma$ and TIMP-2 showed an increasing tendency in Groups 2 and 3 when compared to Group 1. On the other hand, the expression of IL-4 was highest in Group 1. Conclusions: The findings suggest that IFN-$\gamma$ and TIMP-2 may be involved in the periodontal inflammation associated with type 2 DM. IL-4 may be involved in the retrogression of the periodontal inflammation associated with type 2 DM.

Effect of Epigallocatechin-3-gallate on Expression of Chemokines in Human Nasal Mucosal Fibroblasts (Epigallocatechin-3-gallate의 사람 비점막 섬유아세포 케모카인발현에 대한 효과)

  • Cho, Jeong-Je;Leem, Kang-Hyun
    • Korean Journal of Pharmacognosy
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    • v.32 no.4 s.127
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    • pp.280-286
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    • 2001
  • Epigallocathechin-3-gallate (EGCG), the main polyphenol component in green tea, inhibits angiogenesis, urokinase, and matalloproteinases, and EGCG also has the antioxidative property. Recent reports proposed that EGCG may modulate the immune response on allergy or asthma. Human nasal mucosal fibroblasts are a rich source of cytokines, inflammatory mediators, and chemokines. Chemokines are important for the recruitment of leukocytes to sites of infection, which is essential in host defense. The objective of this study was to investigate the effect of EGCG on the expression of the chemokines such as RANTES (regulated upon activation, normal T cell expressed and presumably secreted), eotaxin, and interleukin-8 (IL-8) in human nasal mucosal fibroblasts after stimulation with cytokines like IL-4, tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $interferon-{\gamma}\;(IFN-{\gamma})$. To detect the expression of chemokine genes, RT-PCR was performed. Expressions of RANTES, eotaxin, and IL-8 mRNA stimulated with IL-4 and $TNF-{\alpha}$ were increased, respectively, while the expression of those genes incubated with $IFN-{\gamma}$ was similar pattern compared to control group. Analyses of chemokine genes of cells pretreated with EGCG showed that the expressions of eotaxin, and IL-8 genes stimulated $IFN-{\gamma}$ were higher compared with those not pretreated with EGCG.

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Nitric Oxide Production in Brain Microglial Cells by Taraxacum officinale (포공영(蒲公英)에 의한 뇌 소교세포에서 산화질소 (NO)의 생성)

  • Im, Mi-Yang;Moon, Seok-Jae
    • 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.

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NO Formation of the PMA and LPS-activated Rat Kupffer- and Endothelial Cells in vitro (In Vitro에서 PMA와 LPS로 활성화된 흰쥐 간내 Kupffer-와 Endothelial 세포에서의 NO 형성에 관한 연구)

  • 김기성
    • Biomolecules & Therapeutics
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    • v.3 no.3
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    • pp.188-191
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    • 1995
  • The Present study was undertaken to indicate the major source of NO by liver cells in vitro. Even at early stages of induction or low LPS concentrations, NO was produced at high rates by LPS(Lipopolysaccharide) on the isolated rat kupffer cells. PMA(phorbol 12-myristate 13-acetate) induced NO formation at low rates in the same cells. IFN-${\gamma}$ (Interferon-${\gamma}$) alone had not induced NO formation but it stimulated the effects of LPS. Calcium ionophore A23187 caused no stimulatory effect. It suggests that LPS has especially strong NO inducer on the kupffer cells and its mechanism is related to those on macrophage in other organs. In other nonparenchymal liver cells, sinusoidal endothelial cells were not stimulated to produce NO either by inducers of aortic endothelium(A23187, ATP and ADP) or by effectors of macrophages(LPS, IFN-${\gamma}$. This results suggest that rat liver kupffer cells appear to be the major source of NO by liver cells in vitro. But in vivo, liver endothelial cells may still be capable of producing NO. Furthermore, kupffer cells may produce factors that facilitate NO production by the endothelial cells.

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Effect of Indomethacin on the Lipopolysaccharide-induced Production of Cytokines in Tumor-bearing Mice (암유발 생쥐에서 리포폴리사카라이드에 의해 유도된 사이토카인이 생산에 미치는 인도메타신의 영향)

  • 채병숙
    • YAKHAK HOEJI
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    • v.45 no.6
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    • pp.715-723
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    • 2001
  • Indomethacin is well known as a prostaglandin (PG) E$_2$ synthetase inhibitor which has antipyretic and anti-inflammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1$\beta$, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and interferon (IFN)-${\gamma}$ levels in supernatants, whereas indomethacin did not affect the LPS-increased levels of IL-2 and IFN-${\gamma}$. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1$\beta$, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-increased production of IL- 2 and IFN-${\gamma}$ in tumor-bearing state.

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The Screening of Fermented Medicinal Herbs to Identify Those with Anti-inflammatory Properties

  • Shen, Feng-Yan;Ra, Je-Hveon;Kim, Jin-Ju;Jung, Sung-Ki
    • The Journal of Internal Korean Medicine
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    • v.30 no.1
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    • pp.64-73
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    • 2009
  • Objectives : Consumption of fermented foods has been known to alleviate some of the symptoms of atopy and may limit allergy development, while there are also many medicinal herbs proved to be effective for immunologically-mediated diseases. In this study, we introduced modern zymology to ferment some herbs to see if fermentation has the possibility of increasing the anti-inflammatory effects of medicinal herbs. Interleukin-4 (IL-4) and interferon-gamma $(INF-\gamma)$ have been demonstrated to be the main factors in the pathology of allergic diseases. Methods : We measured the levels of IL-4 and $INF-\gamma$ on concanavalin A-induced BALB/c mice spleen cells, which were subsequently treated with fermented and unfermented herbs. We then compared the fermented groups with unfermented groups to see if the anti-inflammatory effects of the herbs were influenced by fermentation. Results and Conclusions : Our results showed that fermentation had the potential to increase the anti-inflammatory effects of some medicinal herbs, and Astragalus membranaceus and Salvia miltiorrhiza would be the most suitable medicinal herbs for fermentation among the herbs in this study.

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