• Asian-Australasian Journal of Animal Sciences
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• 제26권6호
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• pp.795-803
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• 2013

Various endometrial genes in ruminant ungulates are regulated by conceptus interferon tau (IFNT). However, the effect of each IFNT isoform has not been carefully evaluated. In this study, the effects of 2 IFNT isoforms, paralogs found in utero, and interferon alpha (IFNA) on uterine epithelial and Mardin-Darby bovine kidney (MDBK) cells were evaluated. Expression vectors of the bovine interferon (bIFNT) genes bIFNT1, bIFNTc1, and bIFNA were constructed, and recombinant bIFNs (rbIFNs) were produced by 293 cells. Bovine uterine epithelial or MDBK cells were cultured in the presence or absence of increasing concentrations of each rbIFN for 24, 48, or 72 h. Transcript levels of the IFN-stimulated genes (ISGs) ISG12, ISG15, MX1, and MX2 were analyzed using quantitative reverse transcription-polymerase chain reaction. These messenger RNAs were up-regulated by rbIFN in a time- and concentration-dependent manner. In the epithelial cells, the ISG12 transcript level increased at 48 h after rbIFN treatment but slightly decreased at 72 h, whereas the transcript level of ISG15 increased at 24 h and was maintained through 72 h. Expressions of MX1 and MX2 increased at 72 h after rbIFN treatment. MX1 expression increased in all treatment groups, but MX2 increased only by bIFNTc1. In MDBK cells, the expression of ISG12 was increased by bIFNT1 and bIFNTc1 after 24 and 72 h; however, it was unchanged by rbIFNA. ISG15 increased following the same pattern as that seen in uterine epithelial cells, and MX1 showed a similar expression pattern. MX2 expression was increased by bIFNTc1 treatment in uterine epithelial cells, and its expression was increased by both bIFNT1 and bIFNTc1 in MDBK cells. These results show that epithelial and MDBK cell responses to IFNs differ, suggesting that IFNs possess common functions, but may have acquired different functions following gene duplication.

• 대한본초학회지
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• 제27권1호
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• pp.59-64
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• 2012

Objective : This study was performed to evaluate the effect of Forsythiae Fructus (FF) ethanol extract on inflammatory cytokine production and its underlying mechanisms in mouse macrophages. Methods : Peritoneal macrophages from thioglycollate medium-injected mice were cultured and stimulated with lipopolysaccharide(LPS) or LPS/interferon(IFN)-${\gamma}$ for cytokine measurement and cellular signaling molecule analysis. Results : FF ethanol extract decreased the levels of secreted tumor necrosis factor(TNF)-${\alpha}$ and interleukin(IL)-6 in IFN-${\gamma}$/LPS-stimulated cells in a concentration-dependent manner. FF extract reduced IFN-${\gamma}$/LPS-induced STAT1 phosphorylation and LPS-induced p38 and JNK activation, but not ERK1/2 activity. The extract also inhibited LPS-induced $I{\kappa}B{\alpha}$ degradation through suppression of $I{\kappa}B{\alpha}$ kinase. Conclusions : These results suggest that FF ethanol extract affects the production of TNF-${\alpha}$ and IL-6 through inhibition of activation of STAT-1, $I{\kappa}B{\alpha}$, p38, and JNK.

• Journal of Yeungnam Medical Science
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• 제24권2호
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• pp.129-136
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• 2007

2002년 1월 1일부터 6월 30일까지 비재발성 또는 약한 재발성 마른기침을 주증상으로 영남대학교 의료원 소아과를 내원한 환아들 중 연구의 목적에 동의한 소아를 대상으로 이들에서의 케모카인 IFN-${\gamma}$-inducible protein 10 (IP-10), Macrophage cationic protein 1 and 3 (MCP-1, 3), Interleukin (IL)-8, RANTES, eotaxin 및 Gro-${\alpha}$의 발현 양상을 알아보았다. 1) 대상 환아는 모두 6명(남 3명, 여 3명)으로, 평균 연령은 73.2개월(34개월~122개월)이었다. 2) 케모카인 IP-10, MCP-3는 모든 환아에서, RANTES는 5명에서, IL-8은 3명에서 발현되었다. 3) Eotaxin, Gro-${\alpha}$ 및 MCP-1은 모든 환아에서 전혀 발현되지 않았다. 4) 추적 관찰에 응한 1례에서 회복기에 MCP-3, RANTES 및 IL-8 발현의 감소가 관찰되었다. 단순 기침 환아에서 케모카인 MCP-3, RANTES 및 IL-8 등이 매우 중요한 역할을 하는 것으로 확인되었다. 향 후 이에 관한 더 많은 비교 연구가 필요할 것으로 생각한다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.369-377
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• 2018

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their $6^{th}$ lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor ${\kappa}B$ ($NF-{\kappa}B$) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon ${\gamma}$ ($IFN-{\gamma}$) were evaluated through ELISA. The effects of ISL on the phosphorylation of $I{\kappa}B{\alpha}$, $IKK{\alpha}/{\beta}$ and p65 in $NF-{\kappa}B$ signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. $NF-{\kappa}B$ signaling was inhibited, in which the phosphorylation of p65, $I{\kappa}B{\alpha}$ and $IKK{\alpha}/{\beta}$ were suppressed whereas the level of $I{\kappa}B{\alpha}$ were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, $NF-{\kappa}B$, IL-4 and IL-10 in treating ST.

• 약학회지
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• 제51권1호
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• pp.35-43
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• 2007

To investigate the immunomodulatory roles of cyclic AMP (CAMP) on macrophage- and T lymphocyte-mediated immune responses, CAMP elevating agents were employed and carefully re-examined under the activation conditions of the cells. Various inhibitors tested dose-dependently blocked tumor necrosis factor (TNF)-${\alpha}$ production with IC$_{50}$ values ranged from 0.04 to 300 ${\mu}$M. Of the inhibitors, cAMP-elevating agents showed lower cytotoxicity assessed by lactate dehydrogenase (LDH) release, suggesting less toxic and more selective. In particular co-treatment of dbcAMP with a protein kinase C inhibitor staurosporine displayed the synergistic inhibition of TNF-${\alpha}$ production. The modulatory effect of dbcAMP on TNF-${\alpha}$ and nitric oxide (NO) was significantly affected by treatment time of dbcAMP. Thus, post-treatment of dbcAMP (three hours before LPS) abrogated dbcAMP's inhibitory activity and rather enhanced TNF-${\alpha}$ level up to 60%. In contrast, additional NO production was shown at the co-treatment of dbcAMP with LPS. Unlike simultaneous treatment of phorbol 12-myristate 13-acetate (PMA) and interferon (IFN)-${\gamma}$co-treatment, the combination of dbcAMP with other NO-inducing stimuli did not show drastic overproduction of NO. cAMP elevating agents also diminished splenocyte proliferation stimulated by concanavalin (Con) A, phytohemaglutinin A (PHA) and lipopolysaccharide (LPS). In addition, dbcAMP but not rolipram strongly suppressed CD8$^+$ T cells (CTLL-2). Finally, cAMP elevating agents were differentially involved in regulating CD98-mediated cell-cell adhesion. Thus, dbcAMP and rolipram significantly enhanced the cell-cell adhesion, whereas forskolin blocked. Therefore, our results suggest that CAMP elevating agents participate in various immune responses mediated by macrophages and T cells with a different fashion depending on cellular environments and activation signals.

• 사상체질의학회지
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• 제13권1호
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• pp.61-69
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• 2001

사상의학적 견지에서 태음인(太陰人)의 중풍, 치매와 같은 신경계질환에 다용되고 있는 열다한소탕(熱多寒少湯)은 최근에 그 임상적 효과를 뒷받침할 다각적인 연구들이 이루어지고 있음에도 불구하고 그 정확한 약리학적 기전에 대해서는 밝혀지지 않고 있다. 본 연구에서는 인간성상세포를 이용하여 열다한소탕(熱多寒少湯)이 substance P (SP)와 lipopolysaccharide (LPS)에 의해 유도되는 다양한 세포활성물질의 분비량의 조절을 검토함으로써 열다한소탕(熱多寒少湯)의 약리기전을 면역학적 측면에서 보다 세밀하게 살펴보고자 하였다. 열다한소탕(熱多寒少湯) 수침액은 인간 뇌 성상세포로 부터 LPS와 SP의 동시자극에 의해 생성되는 세포활성물질중 interleukin (IL)-1, IL-4, IL-6 및 tumor necrosisfaccor-${\alpha}$ (TNF-${\alpha}$)의 분비를 농도의존적으로 억제했다. 그러나 interferon-${\gamma}$ (IFN-${\gamma}$) 및 IL-2의 분비 조절에는 영향을 미치지 않았다. 그리고 항 IL-$1{\beta}$ 항체에 의해 SP 유도성 TNF-${\alpha}$ 분비의 증가가 억제되기 때문에 IL-1은 TNF-${\alpha}$ 증가를 매개하는 역할을 하는 것으로 사료된다. 이상의 결과는 열다한소탕(熱多寒少湯)에 의한 급성기 중풍환자 치료 효과가 뇌 성상세포로부터 분비되는 세포활성물질의 조절과 밀접한 관련성이 있다는 것을 암시하고 있다.

• Parasites, Hosts and Diseases
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• 제51권1호
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• pp.133-137
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• 2013

This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

• Molecules and Cells
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• 제41권4호
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• pp.271-281
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• 2018

IFIT1 (also known as ISG56) is a member of the interferon-inducible protein with tetratricopeptide repeats (IFITs) family. IFITs are strongly induced by type I interferon (IFN), double-stranded RNA and virus infection. Here, we investigated IFIT1 expression in human umbilical vein endothelial cells (HUVECs) and in human bronchus epithelial cells (BEAS-2Bs) induced by the H9N2 virus and inactivated viral particle at different time points. We also investigated the effect of H9N2 virus and viral particle infection on $IFN-{\alpha}/{\beta}$ production, and assessed whether hemagglutinin or neuraminidase protein induced IFIT1 expression. Results showed that both H9N2 virus infection and viral particle inoculation induced the expression of IFIT1 at mRNA and protein levels in the two cell lines. Hemagglutinin or neuraminidase protein binding alone is not sufficient to induce IFIT1 expression. Surprisingly, the expression patterns of IFIT1 in response to H9N2 virus and viral particles in the two cell lines were opposite, and production kinetics of $IFN-{\alpha}/{\beta}$ also differed. An additional finding was that induction of IFIT1 in response to H9N2 virus infection or viral particle inoculation was more sensitive in HUVECs than in BEAS-2Bs. Our data offers new insight into the innate immune response of endothelial cells to H9N2 virus infection.

• Journal of Ginseng Research
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• 제29권2호
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• pp.80-85
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• 2005

Antiallergic and antipsoriatic effects of korean Red Ginseng (KRG, steamed root of panax ginseng C.A. Meyer, Family Araliaceae) were measured. Orally administered KRG water extract potently inhibited passive cutaneous anaphylaxis (PCA). KRG water extract also showed the potent inhibition in oxazolone-induced mouse dermatitis, and suppressed mouse ear swelling by $39\%$ at 16 days at a dose of $0.1\%$. KRG water extract reduced the levels of mRNA of cyclooxygenase (COX)-2, $IL-1\beta$, $TNF-\alpha$ and $INF-\gamma$ increased in oxazolone-applied mouse ears, however, did not inhibit that of IL-4. KRG water extract also inhibited iNOS and COX-2 mRNA expression level of RAW264.7 cell induced by lipopolysaccharide. Based on these findings, we suggest that KRG can improve atopic and contact dermatitis by the regulation of $ IL-1\beta$ and $TNF-\alpha$ produced by macrophage cells and $interferon-\gamma$ produced by Th1 cells.

• Toxicological Research
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• 제20권1호
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• pp.21-29
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• 2004

We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.