• BMB Reports
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• 제29권6호
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• pp.530-534
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• 1996

Astrocyte are the major glial cell type in the central nervous system (CNS), and analogous to macrophage, mediates the number of immune responses such as production of cytokines including tumor necrosis factor alpha ($TNF-{\alpha}$) upon activation. $TNF-{\alpha}$ has been implicated in neuroimmunological disorders through killing oligodendrocytes and thus causing demyelination. It has been previously demonstrated that mitogen-activated T cells synthesized a 26 kDa precursor form of $TNF-{\alpha}$ which is bound to the surface of a membrane, and is later secreted as a 17 kDa mature version. In order to examine whether astrocytes would produce the transmembrane form of $TNF-{\alpha}$, astrocytes were stimulated with biological stimuli and the membrane form of $TNF-{\alpha}$ was analyzed by Western blot and FACS analysis. When astrocytes are stimulated with lipopolysaccharide (LPS), $IFN-{\gamma}/LPS$, or $IFN-{\gamma}/IL-1{\beta}$, they were able to express a membrane-anchored $TNF-{\alpha}$ of approximately 26 kDa protein which was immunoreactive to an $anti-TNF-{\alpha}$ antibody, whereas unstimulated astrocytes or astrocytes treated with $IFN-{\gamma}$ or $IL-1{\beta}$ alone was not. Our FACS data were also consistent with the immunoblot analysis. Our result suggests that the membrane form of $TNF-{\alpha}$ expressed by activated astrocytes may cause local damage to oligodendrocytes by direct cell-cell contact and contribute to demyelination observed in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE).

• 약학회지
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• 제49권1호
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• pp.92-96
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• 2005

In order to investigate the effects of bisphenol A (BPA) on cell mediated immune reaction in vitro we examined the allogenic mixed lymphocyte reaction (MLR), splenocytes proliferation (SP) to T cell mitogens and IFN-${\gamma}\;production$. Splenocytes of Balb/c mice ($1.5{\times}10^5$ cells/well) were co-cultured with different numbers of mitomycin C-treated mature dentritic cells (DCs) in presence of BPA (25, 50, 100 ${\mu}M$) and $[^{3}H]$thymidine incorporation (cpm) was measured by scintilation counting. Splenocytes ($2{\times}10^6$ cells/well) were cultured with mitogens, Con A ($2\;{\mu}g/ml$), PHA ($5\;{\mu}g/ml$) and IL-2 ($0.1\;{\mu}g/ml$), or PMA ($5\;{\mu}g/ml$) and INO ($1\;{\mu}g/ml$) in presence of BPA (1, 10, 25, 50, 100 ${\mu}M$) and SP was assessed by MTT assay. $IFN-{\gamma}$ levels in culture supernant were determined by ELISA. At low concentration, BPA slightly increased MLR, SP and $IFN-{\gamma}$ levels, but at higher concentration it showed significant inhibitory effects on these immunological parameters. These results indicate that BPA is able to alternate cell-mediated immune reaction.

• 생약학회지
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• 제36권2호통권141호
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• pp.129-135
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• 2005

Lectins from Allomyrina dichotoma (ADL) and Bombyx mori (BML) were partially purified by physiological saline extraction, ammonium sulfate fractionation, anion exchange column chromatography on DEAE Sephadex A-50 and gel filtration column chromatography on Sephadex G-200. An assay for cytokine expression was carried out by using reverse transcription polymerase chain reaction(RT-PCR). mRNA isolated from PBMC(human peripheral blood mononuclear cells) were stimulated with ADL(O.D.=0.2) and BML(O.D.=0.1) for various times(1,4,8,24,48 and 72 h) and various cytokine mRNA assessed by RT-PCR were shown as follows: The patterns of bands for IL-1 mRNA of BML were very similar with those from ADL and these bands were decreased along the increasing reaction times after showing a strong band at 1 h. However mRNA expressions for IL-2, IL-6, $IFN{\gamma}$ and $TNF{\alpha}$ showed different patterns between ADL and BML. With the effect of ADL, the expression of IL-2 and IL-6 mRNA were continuously detected until 72 h with the strongest band of IL-2 mRNA at 24 h. The strong bands of $IFN{\gamma}$ mRNA were observed from 4 to 8 h but the strongest one of $TNF{\alpha}$ was just observed at 1 h. Meanwhile with BML, the bands for IL-2 and $IFN{\gamma}$ were increased along the increasing reaction times until 72 h. The strongest bands were showed from 4 to 8 h with IL-6 and at 8 h with $TNF[\alpha}$. To verify quantitatively ELISA was used for assay of protein secretions of the cytokine gene with IL-2 and $IFN{\gamma}$ expressed markedly different in RT-PCR. The highest cytokine secretion for IL-2 was demonstrated at 48 h. The production of $IFN{\gamma}$ was markedly increased at 24 h and secreted highest at 72 h. These result suggest that ADL and BML, as inducers of cytokines, can elicit detectable cytokine mRNA from PBMC within the first few hours of stimulation and maintain the production of cytokines for a few days by the methods of RT-PCR and ELISA.

• 한국식품영양과학회지
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• 제35권10호
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• pp.1322-1328
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• 2006

특이적 면역반응을 유도하는 전문 항원제시세포인 수지상세포의 분화와 항원제시기능에 미치는 HemoHIM의 면역기능 증강 효과에 대해 알아보았다. HemoHIM은 수지상세포의 분화/증식 과정에 첨가하였을 경우에 공동자극 분자인 CD40, CD86 분자의 세포 표면 발현량을 증가시키는 것으로 나타났다. 이 수지상세포는 동종항원 반응 T세포를 활성화시켜 IL-2, $IFN-\gamma$ 분비량과 증식반응을 유의하게 증가시켰다. 그리고 HemoHIM을 처리한 수지상세포는 대조군에 비해 OVA항원을 T세포주에 충분히 전달하여 IL-2와 $IFN-\gamma$의 분비량을 유의하게 증가시켰을 뿐만 아니라 T세포주의 증식반응도 유의하게 증가시켰다. 따라서 HemoHIM은 생체 내의 특이적 면역반응을 유도하는 수지상세포의 기능을 강화하는 면역기능 조절제로서 사용이 가능할 것으로 생각된다.

• Natural Product Sciences
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• 제13권4호
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• pp.322-327
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• 2007

Fresh Rehmanniae radix is known as a traditional medicine with anti-inflammatory and antioxidant activities. However, whether Rehmanniae radix attenuates autoimmune inflammation in lupus models characterized by T cell-dependent autoimmune disease including overproduction of proinflammatory cytokines, loss of T cell tolerance, and B cell hyperactivity remains unclear. We investigated the effect of fresh Rehmanniae radix methanol extracts (RGMeOH) on the in vitro overproduction of proinflammatory cytokines by immune cells from pristaneinduced lupus BALB/c mice. These results showed that RGMeOH remarkably attenuated Con A-increased overproduction of proinflammatory cytokines, such as IL-2, IFN-${\gamma}$, IL-6 and IL-10 by splenocytes from pristaneinduced lupus mice. RGMeOH greatly reduced LPS-induced production of TNF-${\alpha}$ by splenic macrophages from pristane-induced lupus mice, while significantly enhanced LPS-induced production of IL-10 but did not alter IL-6 by splenic macrophages and splenocytes. These findings suggest that RGMeOH may ameliorate lupus systemic inflammatory autoimmunity via down-regulation of TNF-${\alpha}$ and T cell-dependent cytokine production.

• Tuberculosis and Respiratory Diseases
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• 제47권2호
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• pp.172-183
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• 1999

연구배경: 산화질소(${\cdot}NO$)는 여러 세포에서 산화질소 합성효소(NOS)에 의해서 생산되며 다양한 병태생리과정에 관여한다. 여러 cytokine들이 iNOS의 발현을 촉진시키고 산화질소 생산을 증가시킴으로써 염증반응을 증폭시키고 세포와 조직손상을 초래한다고 알려진 바, 과산화수소($H_2O_2$)가 세포내 NOS의 발현과 산화질소형성에 미치는 영향을 알아보고자 하였다. 방법: 마우스 대식세포주 RAW264.7에 여러 가지 cytokine과 세균 내독소 (LPS)로 자극을 준 세포군 이에 더하여 $H_2O_2$, NOS 억제제 (L-NAME) 및 항산화제 (catalase)등을 사용하여 세포를 자극한 후 생성된 산화질소 산화물의 농도를 측정하고 Northern analysis로 iNOS mRNA의 발현정도를 보아 다음과 같은 성적을 얻었다. 결과: Cytokine과 LPS 자극군에서 대조군보다 ${\cdot}NO$ 생산이 높았고, 이 자극군에 $H_2O_2$를 추가로 자극하였을 때 ${\cdot}NO$생산이 2 배 이상 유의하게 높았다. Cytokine 자극군에서 $H_2O_2$의 자극 농도에 따른 ${\cdot}NO$생산은 $H_2O_2$의 농도가 증가할수록 유의하게 증가하였다. LPS와 IFN-$\gamma$ 자극군에서 L-NAME을 같이 자극시에 ${\cdot}NO$의 양은 L-NAME의 농도증가에 따라 유의하게 감소하였고, Cytokine 및 $H_2O_2$자극군에서도 추가로 자극한 L-NAME 의 농도증가에 따라 ${\cdot}NO$의 양은 유의하게 감소하였다. Cytokine과 $H_2O_2$ 자극균에 catalase를 같이 자극 하였을 때 ${\cdot}NO$의 양은 유의하게 감소했고, Mercaptoethanol과 phenanthroline을 전처치하고 LPS와 IFN-$\gamma$ 및 $H_2O_2$로 자극한 군에서 이들의 전처치한 농도가 높을수록 ${\cdot}NO$의 양은 유의하게 Cytokine자극군과 IFN-$\gamma$, LPS 자극군에 $H_2O_2$를 추가 자극 후 Northern analysis 결과 $H_2O_2$는 iNOS mRNA 발현을 현저히 증가시켰다. 결론: 이상의 결과로 과산화수소가 cytokine과 내독소 등으로 자극된 마우스 대식세포에서 산화질소생산에 유의한 증폭효과를 나타냈고, iNOS mRNA 의 발현도 증가시켰음을 확인할 수 있었다.

• 동의생리병리학회지
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• 제21권5호
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• pp.1278-1284
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• 2007

Solanum Iyratum Thunb (Solanaceae) has multiple applications in korean traditional medicine because of its cytotoxic, immunological and anti-inflammatory activities. However, no study on the anti-arthritic activity of Solanum Iyratum Thunb has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production were assessed during CIA(collagen-induced arthritis) model mice in lymph node (LN), in knee joint and spleen, using ELISA. DBA/1j mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with Solanum Iyratum Thunb (SLT) orally at 400, 200 mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. SLT significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IFN-gamma in serum and spleen cell culture supernatant. The erosion of cartilage was dramatically reduced in mouse knees after treatment with SLT. In conclusion, our results demonstrates that SLT significantly suppressed the progression of CIA. This action was characterized by suppression of arthritis index, cartilage erosion and synovial cell infiltration and the decreased production of $TNF-{\alpha}$, $IFN-{\gamma}$, CD4+, CD19+, CD3+/CD69+ cells (in lymph node), CD11b+/Gr-1 + (in knee joint).

• Toxicological Research
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• 제24권1호
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• pp.17-22
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• 2008

Sopungsan (SS) is a traditional Korean decoction used for the treatment of dermatitis. The aim of this study is to confirm whether or not SS has a preventive effect on the development of atopic dermatitis in dinitrochlorobenzene-applied Nc/Nga mice. SS was administered orally to Nc/Nga mice, which led to the remarkable suppression of the development of dermatitis, as determined by a histological examination and the serum IgE levels. Moreover, SS inhibited the production of thymus- and activation-regulated chemokine (TARC) and its mRNA expression in a keratinocyte cell line, HaCaT, which had been stimulated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). Activation of the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) or activator protein-1 (AP-1) is one of key steps in the signaling pathways mediating induction of TARC. In this study, SS selectively suppressed NF-${\kappa}B$ activation which may be essential for TARC expression in $TNF-{\alpha}/IFN-{\gamma}$ treated keratinocytes. The inhibitory effect of SS on NF-${\kappa}B$ activation and TARC production might be associated with the anti-dermatitic effects of SS.

• 대한통합의학회지
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• 제6권2호
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• pp.89-98
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• 2018

Purpose : This study was designed to examine the blood glucose control and increase immunity effects of ${\beta}-glucan$ added cooked barley noodle in streptozotocin-induced diabetes mice with a high-fat diet. Method : Forty-eight male ICR mice (6-week-old) were fed AIN-93 diet for 4 weeks. Mice were divided into six groups: normal, diabetic, cooked barley noodle, ${\beta}-glucan$ (5 %) control and two experimental groups (${\beta}-glucan$ 2.5 % and 5 %, cooked barley noodle contained diet with ${\beta}-glucan$ 2.5 % and 5 % w/w). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (150 mg/kg). Result : Blood glucose level was significantly decreased in groups consuming cooked barley noodles, but no significant difference was exhibited in diabetic and ${\beta}-glucan$ control group. These results were in accordance with the result of oral glucose tolerance test. Blood interfereon $(IFN)-{\gamma}$ was measured in order to identify increase immunity effect of ${\beta}-glucan$ in diabetic mice. Inhibited $IFN-{\gamma}$ concentration was recovered in cooked barley noodle and ${\beta}-glucan$ control group. Moreover, $IFN-{\gamma}$ concentration was dramatically elevated in ${\beta}-glucan$ contained cooked barley noodle groups in a dose dependent manner. Streptozotocin induced AST and ALT activities were decreased in ${\beta}-glucan$ contained cooked barley noodle groups with a strong lipid lowering effect. Conclusion : Although addition of ${\beta}-glucan$n did not give any significant synergistic effect on cooked barley noodle in blood glucose regulation, suppressed $IFN-{\gamma}$ production by STZ was dramatically enhanced by ${\beta}-glucan$ supplementation in a dose dependent manner. Liver function and blood lipid profile were also in accordance with the increase immunity effect of ${\beta}-glucan$. Consequently, ${\beta}-glucan$ added cooked barley noodle can be consumed as good diets for patients with chronic diseases with reduced immunity.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.431-436
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• 2012

Dioscorea species continue to be used in traditional Chinese medicine, and represent a major source of steroid precursors for conventional medicine. In the previous study, We isolated glycoprotein (GDB) from Dioscorea batatas, characterized, and demonstrated immunostimulating activity in C57BL/6 mice. The aim of this study was to investigate the mechanism whereby GDB activates macrophages. Macrophages activation by GDB was investigated by analyzing the effects of GDB on nitric oxide (NO) production, iNOS expression, mitogen activated protein kinase (MAPK) phosphorylation, and transcription factor activation. In the presence of IFN-${\gamma}$, GDB strongly stimulated macrophages to express iNOS and produce NO. Furthermore, the activation of p38 was synergistically induced by GDB plus IFN-${\gamma}$, but SB203580 (a p38 inhibitor) inhibited GDB plus IFN-${\gamma}$-induced p38 activation. This study indicates that GDB is an important activator of macrophages. Furthermore, due to the critical role that macrophage activation plays in innate immune response, the activation effects of GDB on macrophages suggest that GDB may be a useful immunopotentiating agent.