• 대한한의학회지
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• 제19권2호
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• pp.36-49
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• 1998

HERBA SAURURI (HS) has been known to use antiinflammatory drug. To investigated the mechanism of HS-induced NO synthesis, I evaluated the ability of protein kinase C (PKC) inhibitors such as staurosporine (STSN) or polyymyxin B to block HS-induced effects. HS alone had only a small effect, whereas in combination with $rIFN-{\gamma}$, markedly increased NO synthesis in a dose dependent manner. STSN and polymyxin B decreased NO synthesis, which had been induced by $rIFN-{\gamma}$, plus HS. Furthermore, prolonged incubation of the cells with phorbol ester, which down-regulates PKC activity abolished synergistic cooperative effect of HS with $rIFN-{\gamma}$ on NO synthesis. STSN and Polymyxin B potently inhibited HS-induced $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. However, $rIFN-{\gamma}$ plus $TNF-{\alpha}-induced$ NO synthesis was not blocked by STSN or polymyxin B. On the other hand, tyrosine kinase inhibitor, genistein, blocked the NO synthesis and $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. In conlusion, the present results strongly suggest that the capacity of HS to increase NO synthesis from $rIFN-{\gamma}-primed$ macrophages is the result of HS-induced $TNF-{\alpha}$ secretion via the signal transduction pathway of PKC and tyrosine kinase.

• IMMUNE NETWORK
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• 제16권2호
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• pp.109-115
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• 2016

To find the relation between exercise and cytokines, we examined the effect of the training intensity on the levels of cytokines, including interferon-gamma (IFN-γ), interlukine-4 (IL-4) and interlukine-4/interferon-gamma ratio (IL-4/IFN-γ ratio) in female Futsal players. Twelve well-trained female college Futsal players aged 19~22 participated in this study. The athletes completed 30-min of running at 60~65% maximal heart rate [moderate-intensity exercise], and 30-min of running at 75~80% maximal heart rate [high-intensity exercise]. peripheral blood samples were collected 24 h before and 24 h and 48 h after each of the exercise bouts. finding showed that The 30-min bout of moderate-intensity exercise induced a significant increase in IFN-γ (p=0.01) and significant decreases in IL-4 (p=0.001) and IL-4/IFN-γ ratio (p=0.003). And also, 30-min of running at 75~80% maximal heart rate induced increase in IFN-γ (p=0.07) and decreased in IL-4 (p=0.01) and IL-4/IFN-γ ratio (p=0.06) that these changes not significantly. In summary, exercise intensity can effect on the magnitude of changes in cytokines. It seems that moderate intensity exercise enhances cytokine pattern in female college Futsal players.

• Tuberculosis and Respiratory Diseases
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• 제53권3호
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• pp.294-308
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• 2002

연구배경 :결핵은 세포 매개성 면역반응이 병태생리에 중요한 역할을 하는 감염성 질환이다. 결핵균 항원으로 T 림프구가 활성화되면 여러 종류의 cytokine을 분비하며 T 림프구의 분화와 증식, 대식세포의 활성화를 촉진한다. 본 연구에서는 결핵의 중증도, 숙주의 면역상태 및 예후를 반영하는 지표로서 활성화된 T 림프구에서 만들어지는 IL-2의 수용성 수용체인 sIL-2R와 IFN-$\gamma$를 측정하였고 활성화된 대식세포에서 분비되는 neopterin을 측정하여 임상적 유용성을 판정하고자 하였다. 대상 및 방법 :활동성 폐결핵 환자 39명, 결핵성 림프절염 환자 6명의 치료전과 정상 대조군 10명에서 혈청 sIL-2R, neopterin, IFN-$\gamma$를 측정하였고, 결핵성 흉막염 환자 22명에서 치료전 혈청과 흉막액에서 각각 sIL-2R, ADA, neopterin을 측정하였다. 폐결핵 환자 39명을 ATS guidelines에 따라 중증도를 분류하였고, 사망한 1명과 결핵요양소로 전원된 2명을 제외한 36명에서 초치료 2개월 후 혈청 sIL-2R, neopterin과 IFN-$\gamma$를 측정하였다. 결 과 : 1) sIL-2R과 IFN-$\gamma$는 결핵환자에서 대조군에 비하여 증가된 경향을 보였다(p>0.05). Neopterin은 대조군 $4949{\pm}1242.l$ pg/ml, 폐결핵 $29.67{\pm}2132.8$ pg/ml, 결핵성 림프절엽 $3013{\pm}1877.3$ pg/ml, 결핵성 흉막염이 $2035{\pm}1216.4$ pg/ml로 결핵환자에서 대조군에 비하여 감소되는 경향을 보였으며, 폐결핵군과 결핵성 흉막염군에서는 통계적으로 유의하게 감소되어 있었다(p<0.05). 2) 폐결핵의 중증도가 심할수록 sIL-2R와 IFN-$\gamma$는 증가하였고, neopterin은 감소하였다(p<0.01). 3) 폐결핵 환자 36명에서 치료 후 측정한 sIL-2R는 $1071{\pm}l139.4$ U/ml에서 $1023{\pm}1920.9$ U/ml로(p>0.05), IFN-$\gamma$는 $41{\pm}52.8$ pg/ml에서 $22{\pm}23.9$ pg/ml로 각각 감소하였고 (p<0.05), neopterin은 $3158{\pm}2272.6$ pg/ml에서 $3737{\pm}2307.5$ pg/ml로 증가하였다(p>0.05). 이러한 결과는 경증군과 중등증군에 비해 중증군에서 현저한 변화를 보였고 임상적 경과와 상관성을 보였다. 4) 결핵성 흉막염 환자 22명에서 sIL-2R와 ADA는 혈청에 비하여 흉막액에서 유의하게 높은 값을 보였으나(p<0.01), neopterin은 차이가 없었다(p>0.05). 결 론 : 이상의 결과를 바탕으로 특히 중증군에서 치료 후에 sIL-2R, IFN-$\gamma$와 neopterin을 추적 관찰하면 숙주의 면역반응상태, 임상적 중증도 및 치료 반응성을 예측하는데 도움이 될 것으로 생각된다. 또한 결핵성 흉막염 환자에서는 국소적인 변역반웅의 활성화로 흉막액내의 면역학적 지표의 측정이 혈청 검사보다 특이적이며, 흉막액의 sIL-2R의 측정이 결핵성 흉막염의 진단에 유용할 것으로 생각된다.

• Molecules and Cells
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• 제22권2호
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• pp.163-167
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• 2006

Histone deacetylase (HDAC) activity is commonly associated with transcriptional repression. However, there is also evidence for a function in transcriptional activation. Previous studies have demonstrated a fundamental role of deacetylase activity in $IFN{\alpha}$-responsive gene transcription. In the case of type II IFN ($IFN{\gamma}$) results are controversial: some genes require HDAC activity, while transcription of others is repressed by HDAC. To investigate the effect of HDAC on transcription of an $IFN{\gamma}$-activated gene, real-time PCR was used to measure CXCL10 mRNA in Hela cells stimulated with $IFN{\gamma}$ in the presence or absence of the HDAC inhibitor TSA. Chromatin imunoprecipitation combined with real-time PCR was used to check acetylation of histone H4 and recruitment of the STAT1 complex to the ISRE locus of the CXCL10 gene. Activation of CXCL10 transcription in response to $IFN{\gamma}$ was paralleled by a decrease in histone H4 acetylation and an increase in recruitment of the STAT1 complex to the CXCL10 ISRE locus. The transcription of CXCL10 and histone H4 deacetylation were blocked by TSA, but the latter had no obvious affect on recruitment of the STAT1 complex. Our data indicate that $IFN{\gamma}$ and STAT-dependent gene transcription requires the participation of HDAC, as does the $IFN{\alpha}$-STAT pathway.

• 한국임상수의학회지
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• 제27권6호
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• pp.640-646
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• 2010

네오스포라 감염증은 세포내성 원충성 기생충인 Neospora caninum에 의해 발생하는 질병으로 전세계적으로 발생하고 있으며, 소에서는 번식장해로 인한 막대한 경제적 손실을 유발한다. 본 연구는 4 곳의 각기 다른 목장으로부터 N. caninum에 자연 감염된 양성우와 음성우를 포함한 26두의 임신우를 선정하여 2주 내지 4주 간격으로 혈액을 채취하여 호르몬, 항체가, IFN${\gamma}$ 수준과 유산 혹은 분만과의 상관관계를 조사하였다. 유산하지 않은 Neospora 양성우14두의 S/P 평균값은 분만 전 15주에 최고치를 보였고, 이후 분만 때까지 감소하였다. 유산한 양성우 3두의 유산 시기는 각각 인공 수정 후 20주 (142일), 26주 (185일), 28주 (199일)였으며, 이들의 S/P값은 유산 전 13주부터 유산 때까지 높은 수준을 유지하였다. 유산하지 않은 양성우에서 IFN${\gamma}$ 수준은 개체에 따라 그리고 동일한 개체라도 임신기간이 경과함에 따라 다양하게 나타났으며, 유산한 양성우에서 IFN${\gamma}$ 수준은 계속 높은 상태를 유지하거나 또는 유산시점에 근접하여 급상승하였다. Neospora 음성우 9두의 IFN${\gamma}$ 수준은 양성우보다 낮았지만, 그 양상은 유산하지 않은 양성우와 유사하였다. 유산하지 않은 양성우와 음성우에서 평균적인 progesterone수준은 분만 전 7주부터 뚜렷하게 감소하였다. 유산한 양성우에서는 유산 전 5주와 7주의 평균적인 progesterone 수준은 정상 분만한 음성우나 양성우의 분만전 5주와 7주에 측정된 평균 progesterone 수준보다 낮았다. 유산한 양성우에서 17${\beta}$-estradiol의 평균 수준은 유산 시점에 근접할수록 증가하였지만, 혈청내 총양은 유산하지 않은 양성우와 음성우에서 분만시점에 근접하여 측정한 평균 17${\beta}$-estradiol 수준보다 더 낮았다. 이상의 결과로 미루어 보아 Neospora에 감염된 소에서 17${\beta}$-estradiol과 progesterone 수준의 저하는 IFN${\gamma}$ 산생을 증가시켜, 결국에는 유산을 초래할 수 있다고 생각된다.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.130-136
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• 1999

Mouse guanylate-binding protein 3 (mGBP3) is a 71-kDa GTPase which belongs to GTP-binding protein family. The present study showed that the expression of mGBP3 transcript was readily induced in a dose dependent fashion in the macrophage cell line RAW264.7 treated with either $interferon-{\gamma} (IFN-\gamma)$ or lipopolysaccaride (LPS). The expression of mGBP3 protein was also apparent by 4 and 6 h after the treatment of cells with IFN-\gamma (100 U/ml) or LPS ($1{\mu}g/ml$) , and remained at palteau for at least 24 h. Cycloheximide ($10{\mu}g/ml$) had no effect on the $IFN-\gamma-$ or LPS-induced mGBP3 expression, suggesting that the mGBP3 induction did not require further protein synthesis. Interestingly, a protein kinase C (PKC) inhibitor staurosporine (50 nM) abolished the induction of mGBP3 expression by LPS, but not by $IFN-{\gamma}$. These findings suggest that mGBP3 may be involved in the macrophage activation process and both IFN-\gamma and LS induce the mGBP3 expression through distinct signal transduction pathways.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.310.3-311
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• 2002

Macrophages have been known to play an essential role in tumor angiogenesis and produce a number of growth stimulators and inhibitors. Thus macrophages appear to influence every stage of angiogenesis. In this report, TNF-$\alpha$ was able to induce the production of IFN-${\gamma}$ in cancer cell-contanted macrophage. TNF-${\gamma}$ alone released relatively little IFN-${\gamma}$ whereas live tumor cells (3LL) alone releasd IFN-${\gamma}$ markedly from macrophage. (omitted)

• Journal of Korean Neurosurgical Society
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• 제29권4호
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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.

• Journal of Periodontal and Implant Science
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• 제30권4호
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• pp.895-913
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• 2000

It is becoming increasingly clear that human gingival fibroblasts(HGF) may play a role in regulating immune responsiveness in inflammatory periodontal lesions. Stimulation of HGF with locally-secreted T cell cytokine $IFN_{\gamma}$ induces human leukocyte antigen class II(HLA II) expression on HGF, which is one of the characteristic feature of professional antigen presenting cells(pAPC). However, $IFN_{\gamma}$-treated HGF and other nonprofessional antigen presenting cells(npAPC) are known to be ineffective or less effective antigen presenter to resting T cells. This study, therefore, was undertaken in an effort to elucidate the differences in expression of cell surface molecules between npAPC in periodontal tissues, such as HGF and periodontal ligament fibroblasts(PDLF), and pAPC such as monocytes/macrophages. Using flow cytometry, the levels of cell surface expression of HLA-D, ICAM-1, LFA-3, and B7-1, which are involved in antigen presentation, were determined in HGF, PDLF and human myelomonocytic cell line THP-1. $IFN_{\gamma}$ clearly induced HLA-D expression on both of fibroblasts and monocytes dose dependently. However, expression level on monocytes were 4 to 5 times higher than that on fibroblasts, and induction rate was faster in monocytes than in fibroblasts. The levels of ICAM-1 expression on fibroblasts and monocytes were enhanced by $IFN_{\gamma}$ in a dose dependent manner. On the other hand, the expression of LFA-3 molecule, which could be detected in fibroblasts and monocytes without cytokine stimulation, was no more enhanced by addition of $IFN_{\gamma}$. B7-1, important costimulatory molecule in T cell activation and proliferation, was not detected on both of fibroblasts and monocytes even when stimulated with $IFN_{\gamma}$, except on monocytes fully differentiated by pretreatment of PMA and treated by $IFN_{\gamma}$. These results suggest that delayed expression of HLA-D and absence of B7-1 on $IFN_{\gamma}$ - treated fibroblasts may at least in part be involved in the ineffectiveness of fibroblasts as primary APC. And it is postulated that although periodontal fibroblasts may not serve as primary APC in normal periodontium, sustained expression of HLA II on ubiquitous fibroblasts in inflammatory lesions may perpetuate immune responses and produce chronic inflammation and tissue injury.

• Environmental Analysis Health and Toxicology
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• 제20권3호
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• pp.243-248
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• 2005

Mancozeb (MCZ), a polymeric complex of zinr and manganese salts of ethylene bisthiocarbamate, is widely used in agriculture as fungicidel, insecticides, and herbicides. MCZ can be occupationally and environmentally exposed to human and has been reported to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine splenocytes through evaluation of splenocytes cellularity and INF-$\gamma$ synthesis. Splenocytes were examned ex vivo from mice orally treated with various doEes of MCZ for 1 day (acute exposure, 2,100, 5,000, 10,000 mg/kg) or ior 5 consecutive days per week for 4 weeks (subacute exposure,250, 1,000, 1,500 mg/kg/day) fellowed by culture for 2 days in the presence of Con A or PHA plus IL-2. Splenocytes Iron naive mice were cultured with various concentration of MCZ (50, 500, 1,000 ng/ml) in the presence of Con A or PHA plus IL-2 for 2 days in vitro. IFN-$\gamma$ production was decreased with the in vitro exposure to all concentration of MCZ. The spleen cellularity and IFN -$\gamma$ production by splenocytes from MCZ -acutely and - subacutely exposured mice were decreased in comparision with that oi control group.