• IMMUNE NETWORK
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• 제11권5호
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• pp.253-257
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• 2011

Background: The active metabolite (1, 25- dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. Methods: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. Results: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). Conclusion: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

• IMMUNE NETWORK
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• 제11권5호
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• pp.299-306
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• 2011

Background: $CD4^+Fop3^+$ regulatory T cells (Tregs) are needed to maintain peripheral tolerance, but their role in the development of autoimmune arthritis is still debated. The present study was undertaken to investigate the mechanism by which Tregs influence autoimmune arthritis, using a mouse model entitled K/BxN. Methods: We generated Treg-deficient K/BxNsf mice by congenically crossing K/BxN mice with Foxp3 mutant scurfy mice. The arthritic symptoms of the mice were clinically and histopathologically examined. The proportions and activation of $CD4^+$ T cells and/or dendritic cells were assessed in the spleens, draining lymph nodes and synovial tissue of these mice. Results: K/BxNsf mice exhibited earlier onset and more aggressive progression of arthritis than their K/BxN littermates. In particular, bone destruction associated with the influx of numerous RANKL+ cells into synovia was very prominent. They also contained more memory phenotype $CD4^+$ T cells, more Th1 and Th2 cells, and fewer Th17 cells than their control counterparts. Plasmacytoid dendritic cells expressing high levels of CD86 and CD40 were elevated in the K/BxNsf synovia. Conclusion: We conclude that Tregs oppose the progression of arthritis by inhibiting the development of $RANKL^+$ cells, homeostatically proliferating $CD4^+$ T cells, Th1, Th2 and mature plasmacytoid dendritic cells, and by inhibiting their influx into joints.

• IMMUNE NETWORK
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• 제4권3호
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• pp.143-154
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• 2004

Background: CD27 is recently known as a memory B cell marker and is mainly expressed in activated T cells, some B cell population and NK cells. CD27 is a member of tumor necrosis factor receptor family. Like CD40 molecule, CD27 has (P/S/T/A) X(Q/E)E motif for interacting with TNF receptor-associated factors (TRAFs), and TRAF2 and TRAF5 bindings to CD27 in 293T cells were reported. Methods: To investigate the CD27 signaling effect in B cells, human CD40 extracellular domain containing mouse CD27 cytoplamic domain construct (hCD40-mCD27) was transfected into mouse B cell line CH12.LX and M12.4.1. Results: Through the stimulation of hCD40-mCD27 molecule via anti-human CD40 antibody or CD154 ligation, expression of CD11a, CD23, CD54, CD70 and CD80 were increased and secretion of IgM was induced, which were comparable to the effect of CD40 stimulation. TRAF2 and TRAF3 were recruited into lipid-enriched membrane raft and were bound to CD27 in M12.4.1 cells. CD27 stimulation, however, did not increase TRAF2 or TRAF3 degradation. Conclusion: In contrast to CD40 signaling pathway, TRAF2 and TRAF3 degradation was not observed after CD27 stimulation and it might contribute to prolonged B cell activation through CD27 signaling.

• IMMUNE NETWORK
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• 제7권1호
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• pp.18-25
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• 2007

Background: Although glucocorticoids (GCs) are effective in controlling asthma in the majority of patients, a subset of asthmatics fails to demonstrate a satisfactory response, even to systemic GC therapy. This population is referred to as being "steroid-resistant". The actual mechanism underlying steroid resistance in asthma remains to be elucidated. Methods: We have investigated how dexamethasone (DEX) regulates asthmatic phenotypes in a murine model of asthma, in which mice received i.p. immunization twice, followed by two bronchoprovocations with aerosolized OVA with a one-week interval, which we have recently described. Results: Pretreatment with DEX resulted in an inhibition of NF-${\kappa}B$ activation in asthmatic lungs, and also inhibited bronchoalveolar lavage (BAL) levels of NF-${\kappa}B$-dependent cytokines such as TNF-${\alpha}$ and CC chemokines [eotaxin and monocyte chemotactic protein (MCP)-1]. DEX was effective in suppressing airway hyperresponsiveness (AHR) at 10 h, Th2-dependent asthmatic phenotypes such as airway eosinophilia, BAL levels of Th2 cytokines (IL-5 and IL-13), and mucin production. However, DEX failed to suppress BAL levels of CXC chemokines [macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC)] and airway neutrophilia. Conclusion: Airway neutrophilia is among the phenomena observed in patients with severe GC-resistant asthma. This study will provide insight into the molecular basis for airway neutrophila seen in steroid-resistant asthma. Further studies are required to delineate the underlying mechanism of CXC chemokine expression in asthma.

• IMMUNE NETWORK
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• 제7권1호
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• 대한약침학회지
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• 제4권3호
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• pp.23-37
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• 2001

Objective: The purpose of this study is to develop and activate anti-tumor herbal acupuncture for cancer patients in South Korea. Methods: We investigated some literatures on anti-tumor herbal acupuncture which is used in South Korea and China, and made diagrams. Results: The results are summarized as follows. Anti-tumor herbal acupuncture is one of the traditional oriental medical method which is effective for cancer patients. In domestic studies, most of herb materials are belong to action of cooling&detoxification(25.0%) and strengthening body resistance(46.4%) which are proved to have effects of anti-tumor, immune activation and preventing tumor. In China, point injection therapy are used for improving symptoms of cancer patients and hea1ing tumor. Also herbal intravenous injection is used for combination of chinese traditional and western cancer therapy and treating cancer patients variously. Conclusions: From the above results. it is expected that anti-tumor herbal acupuncture is useful to improve clinical symptoms and quality of life(QOL) of cancer patients. Also we must develop new progressive methods of point injection and herbal intravenous injection for treating cancer patients, and advance clinical studies and trials.

• 생명과학회지
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• 제14권3호
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• pp.501-508
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• 2004

전통발효 식품인 간장으로부터 chitinase활성이 높으면서 갈변반응을 일으키는 균주인 CJ-3를 분리하여 갈변반응생성물이 면역기능, 항산화력 및 세포활성에 미치는 영향과 생화학적 특성을 규명하였다. 분리된 CJ-3 균주는 16S rDNA 염기서열분석에 의하여 Bacillus atrophaeus로 동정되었으며 분리된 균주의 분자량은 대략 31.0 kDa으로 colloidal chitin(0.5, 1.0, 2.0%)의 첨가에 의하여 chitinase 활성이 현저히 증가되었다 B. atrophaeus CJ-3에 의해서 유도되는 갈변반응물 200${\mu}\ell$ 첨가로 LPS에 의하여 유도되는 nitric oxide (NO) 활성을 45%까지 감소시켰다. MTT 분석을 통한 세포활성에서도 갈변반응물은 LPS에 의하여 세포활성을 정상수준으로 회복하였다. CJ-3. 균주의 DPPH 전자공여능법에 의한 항산화력은 갈변반응에 의하여 약 55% 증가하였다 . 이러한 결과들은 갈변반응생성물은 면역기능 및 세포활성을 증가시키는 것으로 추정된다. 분리된 균주의 최적 생육조건은 최적온도 37$^{\circ}C$, 최적 pH 7.0 및 염 농도는 9% NaCl농도까지는 잘 생육하는 것으로 나타났으며 분리된 균주의 주요 intracellular 유리아미노산은 glutamate로 나타났다.

• 생명과학회지
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• 제15권5호
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• pp.703-706
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• 2005

본 연구는 Wistar-Koyto Rat과 Spontaneously Hypertensive Rat을 대상으로 10주간의 L-arginine 투여와 규칙적인 수영 훈련을 하였을 때, 심박수, 혈압, 간조직의 eNOS 활성 및 대식세포의 활성수준을 비교 분석하여 고혈압 질환상태에서 심혈관계 및 eNOS 수준에 대한 L-arginine 투여와 훈련의 효과를 규명하는데 목적이 있었다. 결과적으로 고혈압 통제군의 심박수, 혈압, eNOS, 및 대식세포의 활성은 정산군에 비해 현저하게 높은 수치를 보였는데, 이는 고혈압으로 인한 혈관내피세포 손상으로 산화질소 생성기전에 불안정을 초래하여 심혈관계에 부정적인 영향을 주었을 것으로 해석한다. 하지만 L-arginine 투여와 규칙적인 수영훈련은 심박수, 혈압 및 eNOS 수준을 안정 수준으로 회복하였고, 대식세포의 활성 역시 안정화함으로 심혈관계에 긍정적인 영향력을 미치는 것으로 나타났다.

• IMMUNE NETWORK
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• 제12권5호
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• pp.181-188
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• 2012

Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-${\kappa}B$, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-${\kappa}B$-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.

• IMMUNE NETWORK
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• 제14권1호
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• pp.38-44
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• 2014

K/BxN serum can transfer arthritis to normal mice owing to the abundant autoantibodies it contains, which trigger innate inflammatory cascades in joints. Little is known about whether gut-residing microbes affect host susceptibility to autoantibody-mediated arthritis. To address this, we fed C57BL/6 mice with water containing a mixture of antibiotics (ampicillin, vancomycin, neomycin, and metronidazol) for 2 weeks and then injected them with K/BxN serum. Antibiotic treatment significantly reduced the amount of bacterial genomic DNA isolated from fecal samples, in particular a gene encoding 16S ribosomal RNA derived from segmented filamentous bacteria. Arthritic signs, as indicated by the arthritic index and ankle thickness, were significantly attenuated in antibiotic-treated mice compared with untreated controls. Peyer's patches and mesenteric lymph nodes from antibiotic-treated mice contained fewer IL-17-expressing cells than those from untreated mice. Antibiotic treatment reduced serum C3 deposition in vitro via the alternative complement pathway. IL-$17^{-/-}$ congenic C57BL/6 mice were less susceptible to K/BxN serum-transferred arthritis than their wild-type littermates, but were still responsive to treatment with antibiotics. These results suggest that gut-residing microbes, including segmented filamentous bacteria, induce IL-17 production in GALT and complement activation via the alternative complement pathway, which cause the host to be more susceptible to autoantibody-mediated arthritis.