• 한국식품저장유통학회지
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• 제23권3호
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• pp.378-386
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• 2016

DJ#3과 DJ#13은 항염증질환 소재로서 가능성을 확인하고자 국내 전통식품 풀질인증 된장에서 장기간 숙성된장으로 선발된 시료이다. DJ#3과 DJ#13 추출물의 세포독성을 살펴보기 위하여 혈관내피세포를 이용하여 세포의 생존율을 살펴본 결과 DJ#3과 DJ#13 추출물 모두 $100{\mu}g/mL$의 농도까지 전혀 독성을 나타내지 않았다. 또한 DJ#3과 DJ#13 추출물의 항염증 효과를 TNF-${\alpha}$에 의해 활성화된 혈관내피세포에서의 NO 생성, 염증관련 단백질 발현과 mRNA 유전자 발현의 변화를 통하여 확인하였다. 혈관내피세포에 TNF-${\alpha}$를 처리한 결과 NO의 함량이 유의적으로 감소하였다가 DJ#3과 DJ#13 추출물(20, 50, $100{\mu}g/mL$)을 처리하였을 때 유의성은 없으나 증가하였다. 세포배양액내 VCAM-1, ICAM-1 발현을 확인한 결과 혈관내피세포에 TNF-${\alpha}$를 처리한 군에서 증가된 VCAM-1 발현이 DJ#3 추출물 20, $50{\mu}g/mL$에서 유의성 있는 감소를 보였다. 또한 DJ#3 추출물은 NO 생성과 연관 있는 eNOS mRNA의 발현을 농도 의존적으로 증가하였으며, iNOS mRNA의 발현은 농도 의존적으로 감소하였으며 이는 NO 생성 증가가 iNOS의 발현억제를 경유한 것으로 사료된다. 또한 다수의 항염증 약물들의 작용기전이 되는 COX-2의 생성억제를 살펴본 결과 DJ#3 추출물은 TNF-${\alpha}$에 의해 발현되는 COX-2 단백질의 발현을 억제하였음을 확인할 수 있었다. 또한, DJ#3 추출물은 CAMs 단백질 및 mRNA 발현율의 감소됨을 보였다, 이상의 결과로 보아, DJ#3 추출물은 혈관내피세포에서 TNF-${\alpha}$로 유도된 혈관염증을 감소하는 효과를 가지고 있으며, 항염증물질의 연구에 기초 자료로 활용이 가능할 것으로 기대된다. 또한 염증과 관련된 cytokine 및 단백질 발현 메커니즘에 대한 추가적인 연구가 필요할 것으로 판단된다.

• Journal of Korean Dental Science
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• 제6권1호
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• pp.22-26
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• 2013

Purpose: Transglutaminase 2 (TGase 2) is expressed by tumor necrosis factor-${\alpha}$ in various carcinoma. The role of TGase 2 expression in salivary gland tumors is not clear yet. Established slaivary gland tumor (SGT)cell line has been used to study the pathogenesis of salivary gland adenocarcinoma on a cellular level in vitro. The pupose of this study were to examine mRNA expression of TGase 2 in SGT cell line compared to other tumor cell lines, and to apply these results to the pathogenesis of salivary gland tumor. Materials and Methods: After SGT, SCC-15, HN 4, and HeLa tumor cell lines were cultured under preconfl uency, and 3 days after postconfl uency, the cells were harvested for total RNA extraction and cDNA preparation. Result: Reverse transcription polymerase chain reaction for semiquantitative mRNA analysis was done. TGase 2 mRNA expression was not induced by confl uency in all the cell lines. TGase 2 mRNA expression was variable but markedly enhanced in SGT cell line. Conclusion: mRNA expression of TGase 2 should play an important role in the pathogenesis of SGT cell line originated from ductal cell.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3681-3686
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• 2014

In this study, we demonstrated selenium (Se) accumulation in Bifidobacterium longum strain (B. longum) and evaluated the effect of Se-enriched B. longum (Se-B. longum) on tumor growth and immune function in tumor-bearing mice. Analysis using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) revealed that more than 99% of Se in Se-B. longum was organic, the main component of which was selenomethionine (SeMet). In the in vivo experiments, tumor-bearing mice (n=8) were orally administrated with different doses of Se-B. longum alone or combined with cyclophosphamide (CTX). The results showed that the middle and high dose of Se-B. longum significantly inhibited tumor growth. When Se-B. longum and CTX were combined, the antitumor effect was significantly enhanced and the survival time of tumor-bearing mice (n=12) was prolonged. Furthermore, compared with CTX alone, the combination of Se-B. longum and CTX stimulated the activity of natural killer (NK) cells and T lymphocytes, increasing the levels of interleukin-2 (IL-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and the leukocyte count of H22 tumor-bearing mice (n=12).

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.320-323
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• 2011

We conducted this study to investigate whether berberine signifi cantly affects MUC5AC mucin gene expression and mucin production induced by epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) from human airway epithelial cells. Confl uent NCI-H292 cells were pretreated with varying concentrations of berberine for 30 min and then stimulated with EGF, PMA or TNF-${\alpha}$ for 24 h. MUC5AC mucin gene expression and mucin production were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Berberine was found to inhibit the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-${\alpha}$. Berberine also inhibited the production of MUC5AC mucin protein stimulated by the same inducers. This result suggests that berberine can regulate the expression of mucin gene and production of mucin protein, by directly acting on human airway epithelial cells.

• 생약학회지
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• 제25권2호
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• pp.132-139
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• 1994

To investigate the effect of Korean mistletoe on stimulation of macrophage, the activity to induce interleukine-1(IL-1) and tumor necrosis factors-${\alpha}(TNF-{\alpha})$ from murine peritoneal macrophage by its extracts originated from oak was examined. From in vitro analysis of the cytokines using the culture supernatants of macrophages stimulated with its extracts for 1hr, it was found that Korean mistletoe induces IL-1 and $TNF-{\alpha}$ from murine macrophage. Furthermore, both extracts of Korean mistletoes that were extracted with distilled water and 2% acetic acid exhibited a significant activity to induce two cytokines. In the stimulation for 30 min, Korean mistletoe at concentration of $1{\sim}100\;\mu/ml$ showed a significant induction of IL-1 from macrophage until 24 hrs after stimulation, showing maximal activity on $5{\sim}10\;hrs\;at\;10{\sim}100\;\mu/ml$. On the other hand, $TNF-{\alpha}$ was induced on the early period, 2 hrs, after stimulation at a wide range of concentration, $1{\sim}500\;\mu/ml$. In addition, the fraction of Korean mistletoe from 80% saturated ammonium sulphate precipitation showed a significant activity to induce both cytokines from macrophage. The present study demonstrates that Korean mistletoe contains immunoregulatory factors responsible for stimulating murine macrophage to secrete IL-1 and $TNF-{\alpha}$ which play an important role in immune responses, and suggests that the activity of Korean mistletoe to induce two cytokines is functioned by a possible independent stimulation manner.

• Journal of Chest Surgery
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• 제31권5호
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• pp.502-508
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• 1998

인공 심폐기를 이용한 체외순환은 우리 몸에 전신적인 염증반응을 일으키므로 수술후에 여러장기의 기능부전을 초래할수 있다. 이러한 염증반응은 체외순환후 체액성, 세포성 및 보체계등의 면역계가 활성화 되어 전체적인 염증반응을 일으키는 것으로 일부연구에서 보고하고 있으며, 이러한 염증반응에는 Tumor Necrosis Factor-$\alpha$(TNF-$\alpha$)를 비롯한, Interleukin-1, Interleukin-6, Interleukin-8 등의 cytokine등 이 전구물질로써 중요한역할을 하는 것으로 알려져 있다. 본 교실에서는 이러한 cytokine의 유리를 억제함으로 체외순환후 염증반응을 줄일수 있다는 가정하에 항염증작용이 있는 부신피질 호르몬을 체외순환전에 투여함으로서 염증반응이 현저히 감소하는지를 혈청내 TNF-$\alpha$를 측정하여 비교 연구하였다. 1996년 6월부터 1996년 8월까지 심장수술환자 20명에서 전향적 연구를 했다. 10명의 비교군은 수술 하루전, 마취전, 체외순환 시작 5분후, 대동맥 차단시작 5분후, 대동맥 차단 끝나기 5분전, 체외순환 끝나기 5분전, 재관류후 2시간, 4시간, 6시간, 12시간, 24시간 별로 10cc씩 채혈하여 TNF-$\alpha$의 수치를 ELISA 방법으로 측정하였고 10명의 스테로이드군은 마취 1시간전에 부신피질 호르몬(Dexamethasone 1mg/Kg)을 정맥주사하고 채혈은 비교군과 같게 했다. 그리고 양군에서 수술전 심전도 및 혈청내 LDH, CPK 효소치와 백혈구 수치를 측정하고 수술후 1일째, 3일째 재측정하였으며, 수술후 3일째내에 환자의 혈압동태 ,폐기능 상태 및 회복상태를 관찰하여 비교하였다. 환자군 간에 LDH 및 백혈구 수치간에 의미있는 차이는 없었으나 CPK 수치가 수술후 첫째날/세째날 비교군이 1122$\pm$456/864 $\pm$42 이고 스테로이드군은 567$\pm$471/325$\pm$87로 큰 차이를 보였고(P=0.002), CPK-MB 효소는 술후 1일째 비교군이 106.4, 스테로이드군이 29.5로 이의있는 차이를 보여주었으나(P=0.02) 수술후 3일째에는 두 군간의 차이가 없었다. 수술후 72시간 관찰기간중 비교군에서 4명의 환자가 3번 이상의 저혈압으로 처치가 필요했고 38$^{\circ}C$ 이상의 발열은 3명의 환자에서 있었다. 환자군 간에 대동맥 차단시간과 체외순환 시간간에 의미있는 차이는 없었고, 인공호흡기 부착시간과 중환자실 체류기간, 입원기간 비교에 있어 스테로이드군이 적은 수치를 보였으나 통계학적 의미는 없었다. TNF-$\alpha$는 대동맥 차단 5분후부터 체외순환 끝나기 5분전까지 양군에서 현저히 증가하였는데 비교군은 체외순환 끝나기 5분 전에 측정한 수치의 평균은 22.3$\pm$6.8 pg/ml였고, 스테로이드군은 대동맥 차단 끝나기 5분 전에 측정한 수치의 평균은 11.9$\pm$4.7 pg/ml였다. 이상의 연구결과에서 수술전 부신피질 호르몬을 정주함으로 체외순환시 Cytokine의 분비를 억제하여, cytokine으로 인한 심장수술후 발생할수있는 전신적 염증반응을 감소시킬것으로 기대되므로 수술후 환자의 중환자실 체류기간, 입원기간 및 합병증률을 줄일 수 있으리라 생각된다.

• Radiation Oncology Journal
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• 제34권3호
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• pp.223-229
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• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

• Tuberculosis and Respiratory Diseases
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• 제53권6호
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• Archives of Pharmacal Research
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• 제27권10호
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• pp.1073-1079
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• 2004

Interactions of the cell adhesion molecules are known to play important roles in mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), activates the NF-kB signaling pathway, which induces the expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1). In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF-${\alpha}$ in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment with vitamin C resulted in the downregulation of the TNF-${\alpha}$-induced surface expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover, a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF-kB activation and IkB${\alpha}$ degradation induced by TNF-${\alpha}$. Taken together, these results suggest that vitamin C downregulates TNF-${\alpha}$- induced ICAM-1 expression via the inhibition of NF-kB activation.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.293-297
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• 2016

TRAIL, tumor necrosis factor (TNF)-related apoptosis-inducing ligand belongs to one of important cytokine superfamilIES, tumor necrosis factor ($TNF{\alpha}$). TRAIL-2 receptor agonists activate several cell signaling pathways in cells in different manners and could lead to apoptosis or necrosis. Agonistic egg yolk antibodies like IgY which have been developed in a selective manner could activate TRAIL death receptors such as TRAIL-2 (DR5) and thus apoptosis signaling. We here investigated induction of apoptosis in human breast cancer cells (MCF7 cell line) by an IgY produced against an 21 aminoacid epitope of the human TRAIL-2 receptor. As the first step a small peptide of 21 aminoacids choosen from the extracellular domain of DR5 protein was produced with a peptide synthesizer. After control assays and confirmation of the correct amino acid sequence, it was injected to hens immunized to achieve high affinity IgYs. At the next step, the produced IgYs were extracted and examined for specificity against DR5 protein by ELISA assay. Subsequently, the anticancer effect of such IgYs was determined by MTT assay in the MCF7 human breast cancer cell line. The produced peptides successfully immunized hens and the produced antibodies which accumulated in egg yolk specifically recognized the DR5 protein. IgYs exerted significant toxicity and killed MCF7 cells as shown by MTT assay.