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Interferon-gamma susceptibility of HL-60 cells, mononuclear cells of umbilical cord blood and bone marrow (HL-60 세포주, 제대혈 및 골수 단핵구 세포의 interferon-gamma에 대한 감수성에 관한 연구)

  • Cheong, Hee Jeong;Hong, Dae Sik;Kim, Sook Ja;Cheong, Jae Hwa;Lee, Joo Young;Lee, Nam Su;Park, Sung Kyu;Won, Jong Ho;Park, Hee Sook;Kim, Sung Il
    • IMMUNE NETWORK
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    • v.1 no.3
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    • pp.230-235
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    • 2001
  • Background: Finding of the regulation of various gene expression by cytokine including $IFN-{\gamma}$ in hematopoietic stem cell will light up the understanding of pathogenesis of aplastic anemia in various aspects. To study on aplastic anemia, however, we have to circumvent the difficulty of directly obtaining bone marrow stem cells from the patient. Therefore, we tried to find out a cell can replace the bone marrow stem cells for study on cell signaling pathway and regulation of gene expression by $IFN-{\gamma}$. Materials and Methods: HL-60 cells, of 20 ng/mL of $IFN-{\gamma}$. Total RNA was isolated from the cells and RT-PCR of the indoleamine 2,3-dioxygenase (IDO), $IFN-{\gamma}$, TNF-${\alpha}$, $MIP-1{\alpha}$, and $TGF-{\beta}2$ was carried out for the estimation of the gene expression. Results: $IFN-{\gamma}$ induced IDO gene expression of mononuclear cells from umbilical cord blood showed similar pattern as compared to that of bone marrow. Whether $INF-{\gamma}$ was treated or not, $TNF-{\alpha}$ was expressed in both mononuclear cells from umbilical cord blood and bone marrow. However, HL-60 cells showed different expression patterns. HL-60 cells would express neither IDO nor $TNF-{\alpha}$ even under the culture with 20ng/mL of $IFN-{\gamma}$. Conclusion: Our results showed bone marrow can be replaced with mononuclear cells from umbilical cord blood in the study on the relation between aplastic anemia and $IFN-{\gamma}$ including $IFN-{\gamma}$ cell signaling pathway.

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A Study on the Effect of Herbal-acupuncture with Phellodendri Cortex Solution on Collagen-induced Arthritis in DBA/1J Mice (황백약침이 콜라겐 유도 관절염 생쥐에 미치는 영향)

  • Kim, Jae-Young;Lee, Hyun
    • Korean Journal of Acupuncture
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    • v.24 no.2
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    • pp.163-184
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    • 2007
  • Objectives & Methods : The purpose of this study is to observe the effects of Phellodendri Cortex Herbal-acupuncture solution (PC-HAS) at Joksamni (ST36) on collagen II induced arthritis in DBA-1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II, chang of immunocyte count, histological change of CIA mouse joint. Results : 1. In the PC-HA group, arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In the PC-HA group, the change of spleen size, spleen adhesion rate and the knee joint were significantly decreased. 3. The levels of $IL-1{\beta}$, IL-6 and INF- in serum of the CIA mouse were significantly decreased by PC-HA. 4. The levels of IgG, IgM and anti-collagen II in serum of the CIA mouse were significantly decreased by PC-HA. 5. In the CIA mouse spleen cell culture, the levels of IFN- , IFN- / IL-4, IL-10 were significantly decreased by PC-HA, but the level of IL-4 was significantly increased by PC-HA. 6. In the PC-HA group, the ratios of $CD3e^+$ to $CD45R^+$ cell, $CD4^+$ to $CD8^+$ cell and $CD4^+/CD25^+$ cell were similarly maintained as normal group in the CIA mouse spleen cell. 7. In the PC-HA group, $CD4^+CD25^+$ and $CD45R^+/CD69^+$ cell were significantly decreased in the lymph nodes. 8. In the PC-HA group, $CD3^+/CD69^+$ and $CD11b^+/Gr-1^+$ cell were significantly decreased in knee joint. 9. In histology, the cartilage destruction and synovial cell proliferation in the PC-HA group were similar with that of the normal group and the collagen fiber expressions in the PC-HA group were similar with that of the normal group. Conclusions : Form the result above, the results suggest that the PC-HA at ST36 has significant effect on collagen-induced arthritis, and can be put to practical use in the future rheumatoid arthritis clinic.

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Pycnogenol, a Standardized Extract of French Maritime Pine Bark, Inhibited the Transcriptional Expression of Th2 Cytokines by Suppressing $NF-{\kappa}B$ Activation in Primary Splenocytes of C57BL/6 Mice with Murine AIDS (Murine AIDS 감염쥐 splenocytes에서 $NF-{\kappa}B$의 활성화 억제를 통한 pycnogenol의 Th2 cytokines의 mRNA 발현 조절 효과)

  • Lee, Jeong-Min
    • Korean Journal of Food Science and Technology
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    • v.38 no.6
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    • pp.829-834
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    • 2006
  • LP-BM5 murine leukemia retrovirus induces the immune dysfunction by imbalanced secretion of Th1 and Th2 cytokines in the murine AIDS model. In the present study, it was investigated whether pycnogenol (Pyc) administration could deactivate $NF-{\kappa}B$ to regulate the gene expression of Th1 and Th2 cytokines in C57BL/6 mice with murine AIDS. Treatment with Pyc for 12 weeks significantly inhibited the loss of body weight and enlargement of spleen and lymph node usually seen with AIDS. Moreover, Pyc increased the plasma level of Th1 cytokines, IL-2 and $IFN-{\gamma}$, while reducing the plasma level of Th2 cytokines, IL-6, IL-10, and $TNF-{\alpha}$. In primary culture of splenocytes, mRNA expression of Th2 cytokines was suppressed, but that of Th1 cytokines was not affected. The LP-BM5 retrovirus infection stimulated the cytoplasmic activation of $NF-{\kappa}B$ and nuclear translocation of $I-{\kappa}B$, whereas Pyc administration significantly reduced $NF-{\kappa}B$ activation and $I-{\kappa}B$ degradation. These results suggested that the inhibitory effect of Pyc on Th2 cytokines in mice with murine AIDS was dependent on suppression of the $NF-{\kappa}B$ signaling pathway and was not dependent on $INF-{\gamma}$ level, which regulates Th2 cytokines.

Effect of Gongjindan, a Traditional Korean Polyherbal Formula, on the Pharmacokinetics Profiles of Donepezil in Male SDRats (2) - Single Oral Combination Treatment of Donepezil 10mg/kg with Gongjindan 100mg/kg, 1.5hr-intervals with 7-day Repeated Treatment -

  • Kwon, Oh Dae;Chung, Dae-Kyoo;Park, Soo Jin;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.2
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    • pp.139-155
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    • 2013
  • Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

Viral Etiology and Epidemiology of Outpatients with Acute Respiratory Illnesses in Busan: 2007-2008 (부산지역 급성 호흡기 증상으로 외래 방문한 환자의 바이러스 원인과 역학: 2007-2008년)

  • Jeong, Jin Woo;Hwang, Youn Ha;Cho, Kyung Soon;Jung, Myung Ju;Min, Sang Kee;Kim, Seong Joon;Chung, Woo Sik
    • Pediatric Infection and Vaccine
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    • v.17 no.2
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    • pp.130-136
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    • 2010
  • Purpose : The purpose of this study is to identify the viral etiology of acute respiratory illnesses and to determine epidemiology in outpatients in Busan, Korea. Methods : We collected nasal wash samples from 990 patients who visited the hospital for acute respiratory illnesses between January 2007 and December 2008. Extracted DNA or RNA from specimens was used for viral detection by an RT-PCR method. Results : Of a total of 990 samples, viruses were detected in 351 cases (35.5%). The ratio of male to female was 1.6:1 and 93.7% were less than 5 years old. Rhinovirus was detected year-round in 202 cases (57.5%), respiratory syncytial virus from October to March in 57 cases (16.2%), adenovirus year-round in 37 cases (10.5%), influenza virus from December to April in 21 cases (6%), bocavirus from January to August in 15 cases (4.3%), parainfluenza virus from April to July in 9 cases (2.6%), coronavirus from January to July in 7 cases (2%), and enterovirus from June to September in 3 cases (0.9%). Conclusion : We identified the etiology and epidemiology of viruses that caused the acute respiratory diseases that were prevalent in Busan, 2007-2008. Further surveillance will be necessary.

A study on Brain activity induced by electro-acupuncture on Taechung(LR3) and Hapkok(LI4) using functional Magnetic Resonance Imaging (태충(太衝)(LR3).합곡(合谷)(LI4) 전침자극(電鍼刺戟)이 뇌활성(腦活性) 변화(變化)에 미치는 영향(影響) - fMRI를 이용(利用)한 연구(硏究) -)

  • Park, Tae-Gyoon;Kim, Young-Il;Hong, Kwon-Eui;Yim, Yun-Kyoung;Lee, Hyun;Lee, Byung-Ryul
    • Korean Journal of Acupuncture
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    • v.21 no.2
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    • pp.29-46
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    • 2004
  • Objectives and Methods : This study was performed to investigate the effect of electro -acupuncture at four gates(bilateral LR3 and LI4) on brain activity in normal subjects using fMRI. Results and Conclusions : 1. fMRI signal increase by electro-acupuncture at Lt. LR3 was observed in Rt. Middle frontal gyrus in group average as well as more than half of the subjects. 2. fMRI signal decreases by electro-acupuncture at Lt. LR3 were observed in Rt. Superior frontal gyrus, Rt. Middle temporal gyrus, Rt. Cingulate gyrus in group average as well as more than half of the subjects. 3. fMRI signal increases by electro-acupuncture at Lt. LI4 were observed in Lt. Superior frontal gyrus, Lt. Middle frontal gyrus, Lt. Inf. Semi-Lunar Lobule(cerebellum), Rt. Middle frontal gyrus, Rt. Cingulate gyrus in group average as well as more than half of the subjects. 4. fMRI signal decreases by electro-acupuncture at Lt. LI4 were observed in Lt. Middle frontal gyrus, Lt. Inferior frontal gyrus, Lt. Precentral gyrus and Rt. Middle frontal gyrus, Rt. Middle temporal gyrus, Rt. Precuneus, Rt. Inferior frontal gyrus, Rt. Postcentral gyrus in group average as well as more than half of the subjects. 5. fMRI signal increase by electro-acupuncture at Lt. LR3 and Lt. LI4 in group average as well as more than half of the subjects was not observed. 6. fMRI signal decreases by electro-acupuncture at Lt. LR3 and Lt. LI4 were observed in Lt. culmen(cerebellum), Lt. Cingulate gyrus와 Rt. Middle frontal gyrus, Rt. Cingulate gyrus, Rt. Inferior frontal gyrus in group average as well as more than half of the subjects. 7. fMRI signal increases by electro-acupuncture at four gates (bilateral LR3 and LI4) were observed in Lt. Middle temporal gyrus and Lt. Postcentral gyrus in group average as well as more than half of the subjects. 8. fMRI signal decrease by electro-acupuncture at four gates (bilateral LR3 and LI4) were observed in Lt. Middle frontal gyrus, Lt. Precentral gyrus, Lt. Inferior frontal gyrus, Lt. Middle temporal gyrus, Lt. Frontal sub-gyral and Rt. Tuber(cerebellum) in group average as well as more than half of the subjects.

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Modulatory Effect of Four Azulene Derivatives from the Fruiting Bodies of Lactarius hatsudake on Interferon-$\gamma$ Production (젖버섯아재비 자실체로부터 분리한 Azulene계 화합물이 Interferon-$\gamma$ 생성에 미치는 영향)

  • Xu, Guang Hua;Kim, Jae-Wha;Li, Gao;Yoo, Ick-Dong
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.36 no.2
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    • pp.151-156
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    • 2010
  • Investigation of secondary bioactive metabolites from the fruiting bodies of Lactarius hatsudake led to the isolation of four azulene derivatives by means of repeated column chromatography and preparative HPLC, and they were identified as 1-formyl-4-methyl-7-isopropyl azulene (1), lactaroviolin (2), 4-methyl-7-isopropyl-azulene-1-carboxylic acid (3), and 1-formyl-4-methyl-7-(1-hydroxy-1-methylethyl) azulene (4) by their physico-chemical properties and spectroscopic analysis. The isolated compounds were evaluated for the effects on modulation of cytokines in natural killer cell line (NK92 cells). Compounds 1 and 4 strongly inhibited IFN-$\gamma$ production in a dose-dependent manner, corresponding to 101.3 % and 92.7 % inhibition at 400 ${\mu}M$, and 11.9 % and 24.1 % at 100 ${\mu}M$, respectively, whereas compounds 2 and 3 showed weak inhibitory effect on INF-$\gamma$ production, corresponding to 45.9 % and 18.0 % inhibition at 400 ${\mu}M$.

Anti-inflammatory Effects of Pentoxifylline and Neutrophil Elastase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury In Vitro (In Vitro 내독소 유도성 급성 폐손상에서 Pentoxifylline과 Neutrophil Elastase Inhibitor의 항염효과)

  • Kim, Young-Kyoon;Kim, Seung-Joon;Park, Yong-Keun;Kim, Seok-Chan;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak;Kim, Sang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.691-702
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    • 2000
  • Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

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The Effects of the High Pressure Boiled Extracts (HPBE) of the Ogol Chicken with Herbs on the Hormones, Cytokine, Specific Antibody of Serum in the Rat (오골계 증탕액 급여가 흰쥐의 혈중 호르몬, Cytokine 및 특이항체에 미치는 영향)

  • Chae Hyun-Seok;Ahn Chong-Nam;Yoo Young-Mo;Ham Jun-Sang;Lee Jong-Moon;Yoon Sang-Ki;Choi Yang-Il
    • Food Science of Animal Resources
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    • v.24 no.3
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    • pp.283-292
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    • 2004
  • This study was conducted to investigate feeding effects of the high pressure boiled extracts (HPBE) of the Ogol chicken with herbs on glucose, hormones and immunological response (cytokine, specific antibody) of serum in the rat which fed either with normal feed (T$_1$), normal feed + herb HPBE (T$_2$), normal feed + Ogol chicken HPBE (T$_3$), normal feed + mixture of cross-bred Ogol chicken HPBE (T$_4$) hydrolyzed with Flavourzyme 0.1% for 35 days. During experimental period, there was a weak trend to have a higher glucose content for the T$_4$ group with 102.27${\pm}$5.95 mg/dL, but it was not significantly higher than other treatments. For insulin level, T$_1$ group showed numerically a slightly higher level with 6.79${\pm}$4.64 ${\mu}$IU/mL, but the difference was not significant in statistic term due likely to a large variation in comparison with other treatments. The treatments did not significantly alter testosterone level in rat plasma with 1.09, 1.46, 0.98, 1.13 ng/mL in T$_1$, T$_2$, T$_3$ and T$_4$, respectively. T$_4$ treatment increased the aldosterone level to a significantly (p<0.05) higher level (273.33 ng/dL) than other treatments. The extract treated rat showed a tendency in the cortisol level of lower levels than the control group, particularly, it was significantly (p<0.05) lower in T$_3$ group than other groups. T$_3$ and T$_4$ groups showed higher levels for interlukin-4 (IL-4) and anti-BSA IgG in immune cells and plasma. T$_2$, T$_3$ and T$_4$ treatments showed a slightly higher levels in v-interferon (INF-r) than the control, with a greater effect for T4 treatments. These results suggested that HPBE of the cross-bred Ogol chicken hydrolyzed with Flavourzyme increased immunological activity and decreased the concentration of cortisol and aldosterone hormones.

The Functional and Genetic Defects of IFN-${\gamma}$ Receptor in the Patients with Tuberculosis (결핵환자에서 IFN-${\gamma}$ 수용체의 기능적 및 유전적 이상에 관한 연구)

  • Park, Gye-Young;Hwang, You-Jin;Lim, Young-Hee;An, Chang-Hyeok;Park, Jeong-Woong;Jeong, Seong-Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.497-505
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    • 2002
  • Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.