• IMMUNE NETWORK
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• 제3권1호
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• pp.61-68
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• 2003

Background: Fibroblast functions both as a structural element and as a vital immunoregulatory cell. Fibroblasts regulate inflammation through governing of chemokine expression. In order to elucidate the mechanisms by which the expressions of chemokines were regulated, the co-stimulatory effects of Th1 and proinflammatory cytokines were compared using nasal mucosal fibroblasts. Methods: Human nasal mucosa was obtained from surgery for septal deviation and the growth of fibroblasts was established. Fibroblasts from 4th to 6th passage were stimulated with various combinations of cytokines. To inhibit selected signaling pathways, fibroblasts were pretreated with cyclosporin A, wortmannin, staurosporine, and dexamethasone prior to the stimulation with cytokines. The supernatants were collected and chemokines were detected with a sandwich enzyme-linked immunosorbent assay. Results: $TNF-{\alpha}/IFN-{\gamma}$-induced production of RANTES was inhibited by all inhibitors used. MCP-1 was produced constitutively and $TNF-{\alpha}$-induced or $TNF-{\alpha}/IFN-{\gamma}$-induced production of MCP-1 was not inhibited by cyclosporin A or wortmannin, but by stauroporine or dexamethasone. All inhibitors used in this experiment inhibited $TNF-{\alpha}/IFN-{\gamma}$-induced or $IL-1{\beta}/IFN-{\gamma}$-induced production of MCP-2 in nasal mucosal fibroblasts. Although staurosporine or dexamethasone showed strong inhibitory effects, cyclosporin A or wortmannin did not inhibit the production of MCP-3 by $IL-1{\beta}/IFN-{\gamma}$ treatment. Conclusion: Chemokines were strongly induced by stimulation of cytokines in combination and showed different pattern of inhibition by the inhibitors. Therefore, it was assumed that cytokines acted on multiple pathways or on unknown pathways which converged to gene-specific transcription factors.

• 한방안이비인후피부과학회지
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• 제11권1호
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• pp.1-22
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• 1998

During the last few years, nitric oxide(NO) as a potent macrophage-derived effector molecule against a variety of bacteria, parasites, and tumors has received increasing attention. More recent studies suggest that NO also has antiviral effects in both murine and human cells. The objective of the current study was to determine the effect of Yongdamsagantang(YST) on the production of NO. Stimulation of mouse peritoneal macrophages with YST after the treatment of recombinant $interferon-{\gammer}(rlFN-{\gammer})$ resulted in the increased NO synthesis. YST had no effect on NO synthesis by itself. When YST was used in combination with $rIFN-{\gammer}$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of YST on NO synthesis was shown 6 hour after treatment with $rIFN-{\gammer}$. This increase in NO synthesis was reflected as increased amount of inducible NO synthase(iNOS) protein. NO production was inhibited by $N^G-monomethyl-L-arginine$. The increased production of NO from $rIFN-{\gammer}$ plus YST-stimulated cells was decreased by the treatment with staurosporin. In addition, synergy between $rIFN-{\gammer}$ and YST was mainly dependent on YST-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. These results suggest that the capacity of YST to increase NO production from $rIFN-{\alpha}-primed$ mouse peritoneal macrophages is the result of YST-induced $TNF-{\alpha}$ secretion.

• 대한한의학회지
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• 제24권1호
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• pp.54-64
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• 2003

Objective : To investigate immune enhancing effects of Boummyunyuck-dan (BMD) Methods : In this study I investigated the effect of BMD on cell proliferation and viability. In addition, I investigated production of cytokines (IL-2, IL-4 and $IFN-{\gamma}$), NO, and $TNF-{\alpha}$ in human T-cell leukemia, MOLT-4 cells. The cells were cultured for 24h in the presence or absence of BMD. Result : BMD increased the cell viability by 15% (P<0.05) and enhanced IL-2, IL-4 and $IFN-{\gamma}$ production compared with media control in a dose-dependent manner (P<0.01) at 24h. BMD also increased mRNA and protein expression levels of $IFN-{\gamma}$ in MOLT-4 cells. In addition, I also assessed the effects of BMD on production of NO and $TNF-{\alpha}$ from the peritoneal macrophages because NO and $TNF-{\alpha}$ as a potent macrophage-derived immune reaction regulatory molecule has received increasing attention. However, BMD had no effect on NO and $TNF-{\alpha}$ production in the cells. Conclusion : These data indicate that BMD has some immune-enhancing effect, and that its action may be due to the proliferation and cytokine production of T cells.

• 한국약용작물학회지
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• 제15권5호
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• pp.324-328
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• 2007

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $Interferon-{\gamma}\;(IFN-{\gamma})$ production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased $IFN-{\gamma}\;and\;TNF-{\alpha}$ production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

• 약학회지
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• 제45권5호
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• pp.557-564
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• 2001

To determine effects of zinc on lipopolysaccharide (LPS)-induced production of proinflammatory cytokines and Iymphokines in tumor-bearing ICR mice, this study has been investigated. Zinc chloride (Zn) at doses of 1 mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS greatly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, in both serum and splenic supernatants compared with those in controls. However Zn strongly decreased LPS-increased production of TNF-$\alpha$ and IL-1$\beta$ in spleenic supernatants compared with those in controls and insignificantly also reduced in serum. LPS insignificantly decreased IL-2 levels in spleenic supernatants compared with those in controls but significantly increased interferon (IFN)-${\gamma}$ levels. Zn didn't affect IL-2 production in splenic supernatants compared to controls but significantly enhanced the LPS-decreased production of IL-2. Zn significantly increased IFN-${\gamma}$ levels in splenic supernatants compared to controls and did not affect the LPS-increased production of IFN-${\gamma}$. These findings suggest that Zn may strongly attenuate the LPS-induced pathogenesis of proinflammatory cytokines in tumor-bearing state and significantly up-regulate the LPS-induced function of T cells to produce IL-2 with maintaining normally the LPS- increased levels of IFN-${\gamma}$.

• 대한약침학회지
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• 제10권2호통권23호
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• pp.31-40
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• 2007

Objective : The aim is to examine the effect of Soyeum Pharmacopuncture (SPP) on collagen-induced arthritis (CIA) in DBA/1OlaHsd mice. Methods : To determine the effect of SPP on chronic IFNlammatory joint disease, we induced CIA in DBA/1OlaHsd mice by immunization with bovine type II collagen. Animals were treated with intraperitoneal injection doses of 2 mg/kg of SPP, beginning 3 days before the expected onset of disease symptoms. Inhibitory Effects of SPP were observed by serum levels of TNF-${\alpha}$, and IFN-${\gamma}$,,, or cell proliferation in the spleen cell culture and histological examination of knee joint. Results : In the CIA Mice, serum levels of TNF-${\alpha}$, and IFN-${\gamma}$,, production in the spleen cell culture were reduced. At the histopathological examination of knee joint, chondropathy of cartilage in the synovial joint in the SP group was repaired while compared with control group. Conclusion : These results suggest that the SPP may be effective for the prevention and treatment of rheumatoid arthritis disease.

• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제6권2호
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• pp.152-160
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• 2003

목 적: 소아의 만성 B형 간염 치료에 interferon-${\alpha}$의 일정한 치료 효과가 보고되고 있다. 저자들은 interferon-${\alpha}$의 용량 차이에 따른 치료 효과 및 초치료와 재치료에 따른 치료 효과에 차이가 있는지 비교해 보았다. 방 법: 1990년 3월부터 1999년 8월까지 경북대학교병원 소아과에 내원하였던 환아(2~14세) 중 6개월 이상 HBsAg, HBeAg 및 HBV DNA가 양성이고, 혈청 ALT치가 상승되어 있는 51명의 환아를 대상으로 27명에게 interferon-${\alpha}$ $3MU/m^2$ ($2.66{\pm}0.66\;MU/m^2$)를 투여하였고 24명에게는 $6\;MU/m^2$ ($4.45{\pm}0.94\;MU/m^2$)을 주 3회씩 6개월(6~12개월)간 피하 혹은 근육 주사하였다. interferon-${\alpha}$ 초치료 평균용량은 $3.50{\pm}1.20\;MU/m^2$이었고 평균 치료 기간은 7개월(6~12개월)이었다. 초치료에 반응이 없었던 환아 중 12명을 대상으로 다시 interferon-${\alpha}$ 재치료를 시행하였다. 재치료 평균 용량은 $3.62{\pm}1.51\;MU/m^2$이었고 평균 치료 기간은 7개월(6~12개월)이었다. 용량 차이를 보인 두 군 사이에 성별, 연령, 치료기간, 치료전 ALT치와 HBV DNA 등에서는 통계학적으로 유의한 차이가 없었으며 초치료, 재치료 두 군간에도 유의한 차이가 없었다. 결 과: 치료 시작 1년 후 시점에서 interferon $3\;MU/m^2$로 치료한 27명 중 11명(41%)에서 ALT의 정상화를 보였고 9명(33%)에서 HBeAg이 anti-HBe로 혈청전환이 되었다. 한편 $6\;MU/m^2$ 치료군 24명 중 에서는 12명(50%)에서 ALT의 정상화를 보였고 7명(29%)에서 혈청전환이 되었는데 두 군 사이의 치료성적에는 통계학적으로 유의한 차이가 없었다. Interferon $3\;MU/m^2$ 치료군에서 발생한 부작용으로는 발열 14례(52%), 백혈구 감소증 10례(37%)였으며 모든 경우에서 특별한 조치 없이 회복되었다. 한편 interferon $6\;MU/m^2$ 치료군에서는 발열 16례(67%), 백혈구 감소증 8례(33%), 혈소판 감소증 1례(4%), 갑상선 기능 저하증 2례(8%)가 있었다. 치료와 관련된 부작용도 두 군 간에 통계학적으로 유의한 차이가 없었다. Interferon-${\alpha}$ 초치료군 51명 중 23명(45%)에서 ALT의 정상화를 보였고 16명(31%)에서 혈청전환이 있었으며 재치료군은 12명 중 3명(25%)에서 ALT의 정상화 및 혈청전환이 있었다. 결 론: Interferon-${\alpha}$ $3\;MU/m^2$ 치료군과 $6\;MU/m^2$치료군을 비교했을 때 ALT의 정상화 및 혈청전환에서 의미 있는 치료 효과의 차이를 찾을 수 없었다. interferon-${\alpha}$ 재치료는 초치료만큼의 효과가 있음을 보여주었다.

• Radiation Oncology Journal
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• 제15권3호
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• pp.175-186
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• 1997

목적 : 방사선조사가 세포내재성 병원균인 Listeria monocytogenes (LM)의 감염에 미치는 영향과 함께 감염면역과 밀접한 관계가 있는 대식세포에서의 $TNF-\alpha$ 및 Nitric oxide (NO) 생산능의 변화와 비장세포에서의 $IFN-\gamma$ 및 IL-2생산능에 미치는 영향을 알아보고자 본 실험을 시행하였다. 대상 및 방법 : 실험동물로는 BALB/c 마우스를 사용하였으며 Co-60 원격치료기를 이용하여 방사선을 조사하였다. LM감염에 미치는 영향을 관찰하기 위해서 방사선조사 1일후 $10^5$의 LM균을 복강내에 주사하고 1일, 3일, 5일후에 비장조직에서 LM생균수를 측정하였다. 방사선조사가 마우스의 생체내에서와 시험관내에서의 $TNF-\alpha$의 생산능에 미치는 효과를 관찰하기 위해서 각각 LPS로 유도하여 L929/Actinomycin D assay에 의해 $TNF-\alpha$량을 측정하였다. $IFN-\gamma$의 생성능은 방사선조사후 비장을 적출하여 비장세포액을 제조하여 Concavalin A (Con-A)로 자극한 후 정량검사를 하였다. IL-2의 생성능은 $IFN-\gamma$실험에서와 같이 비장세포를 얻어서 Con-A로 자극하여 CTLL-2세포의 성장촉진능력을 관찰함으로써 판정하였다. 방사선조사가 복강내 대식세포에서 생산되는 NO에 미치는 영향도 관찰하였다. 결과 : 방사선 (300cGy)을 조사한 군에 LM을 감염시킨 1일후 비장으로부터 검출되는 생균수는 대조군에 비해 감소하였으나 감염 3일 5일후의 생균수는 대조군에 비하여 오히려 증가하였다. 시험관내 복강대식세포에 방사선 (100-850cGy)을 조사하면 1일후 생산되는 $TNF-\alpha$의 양은 대조군에 비하여 증가하였으나, 방사선조사 (100-600cGy) 5일후 수집된 복강대식세포에 의한 $TNF-\alpha$의 생산은 오히려 감소하였고. 방사선조사 (300cGy)후 LM감염시 5일후 유도된 생체내 $TNF-\alpha$의 생산도 대조군에 비해 감소하였다. 방사선 (300cGy)을 조사한 마우스로부터 적출한 비장세포로부터 생산되는 $IFN-\gamma$와 IL-2의 양은 대조군에 비해 감소하였다. NO의 양은 100cGy 및 300cGy조사시 대조군에 비해 증가하였으며 그 이상 조사량을 증가하면 점차 감소하였다. 결론 : 방사선조사후 세포내재성 병원균인 LM감염에 대한 초기 저항성의 증가와 감염중반이후의 저항성 감소는 대식세포에서의 초기 $TNF-\alpha$ 생산능 증가후 감소, 그리고 T림프구에서의 $IFN-\gamma$및 IL-2 생산능 감소와 관련이 있을 것으로 사료된다.

• 동의신경정신과학회지
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• 제15권2호
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• pp.89-101
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• 2004

Objective : The present experiments were designed to study on the immune-enhancing effect of Mountain grown ginseng, Mountain cultivated ginseng, and Panax ginseng Method : In order to compare the immune-enhancing effect of moutain grown ginseng, moutain cultivated ginseng and Panax ginseng, the study was done through the forced swimming test (FST), measurement of T helper Th1, Th2 cytokines and fatigue related factors. Result : Moutain grown ginseng and panax ginseng decreased the immobility time in the FST compared to the control. Glucose, blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH) and Total-protein (T-protein) in serum were investigated. The serum achieved from ginseng administered mouse showed higher BUN, T-protein than the control. moutain grown ginseng administered group showed lower LDH than the control group. moutain grown ginseng administered mouse showed higher glucose than the control. Creatinine was same in either experimental or control group. Ginseng-induced cytokine production in human T-cell line, MOLT-4 cells and mouse peritoneal macrophages were compared. Moutain cultivated ginseng (10-4 dilution) and panax ginseng (10-3 dilution) were increased the interferon $IFN-{\gamma}$ production compared with media control (about 1.6-fold P<0.05) at 48 h. Moutain grown ginseng (10-4 dilution) was increased the $IFN-{\gamma}$ and interleukin IL-4 production compared with media control (about l.4-fold for $IFN-{\gamma}$ and 1.6-fold for IL-4 P<0.05) at 48 h. Moutain grown ginseng (10-3 dilution) and moutain cultivated ginseng (10-4 dilution) were increased the turmor necrosis factor $TNF-{\alpha}$ production compared with $rIFN-{\gamma}$ treated cells (about 1.9-fold for $TNF-{\alpha}$ P<0.05), respectively. Moutain cultivated ginseng (10-3 dilution) was increased the IL-12 production compared with $rIFN-{\gamma}$ treated cell (about 1.7-fold for IL-12 P<0.05). Conclusion : These data suggest that three different three kinds of ginseng act on immune responses in different aspects.