• The Korean Journal of Physiology and Pharmacology
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• 제8권5호
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• pp.273-280
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• 2004

Nitric oxide (NO) has been suggested to act as a mediator of cytokine-induced effects of turn over of bone. Activation of the inducible nitric oxide synthase (iNOS) by inflammation has been related with apoptotic cell death in osteoblast. YS 49, a synthetic isoquinoline alkaloid, inhibits NO production in macrophages activated with cytokines. In the present study, we investigated the molecular mechanism of YS 49 to inhibit iNOS expression in ROS 17/2.8 cells, which were activated with combined treatment of inflammatory cytokines $(TNF-{\alpha},\;IFN-{\gamma})$ and lipopolysaccharide (LPS). Results indicated that YS 49 concentration-dependently reduced iNOS mRNA and protein expression, as evidenced by Northern and Western blot analysis, respectively. The underlying mechanism by which YS 49 suppressed iNOS expression was not to affect iNOS mRNA stability but to inhibit activation and translocation of $NF-_kB$ by preventing the degradation of its inhibitory protein $I_kB_{\alpha}$. As expected, YS 49 prevented NO-induced apoptotic cell death by sodium nitroprusside. Taken together, it is concluded that YS 49 inhibits iNOS expression by interfering with degradation of phosphorylated inhibitory $_kB_{\alpha}\;(p-I_kB_{\alpha})$. These actions may be beneficial for the treatment of inflammation of the joint, such as rheumatoid arthritis.

• IMMUNE NETWORK
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• 제3권1호
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• pp.69-77
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• 2003

Background: Celecoxib, a COX-2 specific inhibitor, has recently been used for the treatment of rheumatoid arthritis. However, the molecular and cellular mechanisms of celecoxib against RA inflammation remain to be defined. To elucidate the action mechanism of celecoxib on inflammatory cells, we investigated the effect of celecoxib on the production of two important mediators of inflammation, nitric oxide and PGE2 Methods: RAW 264.7 cells stimulated with LPS were preincubated with various concentrations of celecoxib (from $10^{-8}$ to $10^{-5}$ M) and $10{\mu}M$ hydrocortisone, respectively. The production of NO and PGE2, the end products of iNOS and COX-2 genes, were estimated in culture supernatants by Greiss method and EIA, respectively. The expression of iNOS gene, COX-2 gene, $NF-{\kappa}B$, and $I-{\kappa}B$ were determined by RT-PCR and western blot analysis. Results: Celecoxib and hydrocortisone inhibited the production of NO and PGE2 in dose dependent manner, when RAW 264.7 cells were stimulated with LPS. The expression of iNOS was also down-regulated by celecoxib and hydrocortisone. Interestingly, COX-2 gene differentially expressed according to the dose of celecoxib, a decrease with lower dose ($10^{-8}$ M) but an increase with higher dose ($10^{-5}$ M). $NF-{\kappa}B$ binding activity was decreased by lower dose of celecoxib, whereas was not affected by higher dose of it. The expression of $I-{\kappa}B$ was suppressed by higher dose of celecoxib. Conclusion: The celecoxib strongly suppressed the production of NO and PGE2 in LPS-stimulated RAW264.7 cells. The decrease of NO seems to be linked to the inhibition of iNOS by celecoxib. The lower and higher dose of celecoxib differentially regulated the COX-2 expression and $NF-{\kappa}B$ activity.

• IMMUNE NETWORK
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• 제14권1호
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• pp.21-29
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• 2014

Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

• 생명과학회지
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• 제26권11호
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• pp.1345-1354
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• 2016

원형탈모증은 흔하게 발병하고 두피와 전신에 모발의 탈락을 일으키는 모낭조직 특이 자가면역질환이다. 모낭은 자체적으로 면역체계와 내분비 환경을 가지고 각 모발주기 단계에 따라 다른 면역 상태를 나타내는 특이한 기관이다. 성장기 모낭의 면역특권의 파괴는 모낭상피 MHC class I 발현과 자가반응성 CD8+T세포에 대한 자가항원 발현을 유도하는 자가면역의 공격을 일으키고 원형탈모증을 유발한다. 임상적 실험적 연구에 의하면, 심리적 스트레스도 모낭 면역/호르몬 체계에 영향을 미쳐 원형탈모증의 유도에 관여할 수 있다고 지적한다. 원형탈모증의 핵심적인 병리기전은 면역특권 수호자(ACTH, ${\alpha}-MSH$와 $TGF-{\beta}$ 등), 자연살해세포그룹 2D-양성(NKG2D+) 세포(NK 세포와 CD8+T 세포 등)와 스트레스 호르몬(CRH와 substance P)과 관련되어 있다. 효과적인 치료법은 여전히 요구되고 있다. 앞으로 치료목표 중의 하나는 스트레스를 포함한 모낭 면역특권을 개선하는 것일 것이다. 최근 연구는 건선, 아토피피부염, 류마티스 관절염 같은 다른 자가면역질환에서 사용되는 JAK억제제와 면역조절제, Tregs, 혈소판풍부혈장요법, 스타틴과 프로스타글란딘 유사제가 원형탈모증에 효과적이라고 보고하였다. 본 논문은 모낭주위 내분비/면역과 관련된 발병기전에 대한 새로운 이해와 원형탈모증의 새로운 치료법에 대해 고찰하였다.

• 동의생리병리학회지
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• 제16권2호
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• pp.233-238
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• 2002

Moxibustion is one of major healing technique in oriental medicine. It has been widely used in many diseases such as rheumatoid arthritis, Hashimoto disease, breech presentation, etc. However, till now, effects of moxibustion on NK cell activity and relations between sympathetic nerve system(SNS) and the immune alteration induced by moxibustion were not well studied. This study was designed to evaluate effects of moxibustion on NK cell activity and the intervention of SNS in the alteration of NK cell activity induced by moxibustion. Splenic NK cytotoxity was measured in a standard 4-h 51Cr release assay. We measured the NK cytotoxity at after moxibustion stimulation for 1,3,5, and 7 days, and also measured the NK cell cytotoxity after 3 and 7 days burn stimulation with similar temperature. IL-2, IL-4, INF-γ in serum were measured by rat IL-2, IL-4, INF-γ ELISA TEST KIT. To evaluate the effects of sympathectomy on alteration of NK cell cytotoxity, 6-hydroxydopamine(6-OHDA : 5Omg/kg) was used. We showed that NK cell activity of moxibustion stimulation group increased at the 3rd day, and declined at 7th day in comparison with that of contol group. In moxibustion stimulation group, NK cell activity of 3 day stimulation group was significantly higher than sham group. On the contrary, in burn stimulation group, NK cell activity was significantly higher than that of sham groups at 3rd, 7th days. Patterns between moxibustion and burns were different. INF- γ level of 3 days moxibustion stimulation group significantly higher than sham group. IL 2 level among groups were not different. IL-4 was not detected in serum with this method. Sympathectomy abolished the NK cell activity alteration induced by moxibustion. The results suggest that moxibustion induces the alteration of NK cell activity, along with INF-γ and SNS is related to these effects.

• Nutrition Research and Practice
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• 제8권5호
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• pp.501-508
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• 2014

BACKGROUND/OBJECTIVES: Rubus Coreanus Miquel (RCM), used as a traditional Korean medicine, reduces chronic inflammatory diseases such as cancer and rheumatoid arthritis. However, its mechanism has not been elucidated. In this study, we examine the anti-inflammatory effects of RCM and their possible mechanisms using RAW 264.7 cells. MATERIALS/METHODS: Unripe RCM ethanol extract (UE), unripe RCM water extract (UH), ripe RCM ethanol extract (RE), and ripe RCM water extract (RH) were prepared. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (iNOS, COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and NO and $PGE_2$ productions were assessed. To determine the anti-inflammatory mechanism of RCM, we measured NF-${\kappa}B$ and MAPK activities. RESULTS: UE and UH treatment significantly reduced NF-${\kappa}B$ activation and JNK and p38 phosphorylation and reduced transcriptional activities decreased iNOS, COX-2, and pro-inflammatory cytokines expressions, and NO and $PGE_2$ productions. RE and RH treatments reduced IL-$1{\beta}$ and IL-6 expressions through suppressions of JNK and p38 phosphorylation. CONCLUSIONS: In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions. Especially, unripe RCM showed strong anti-inflammatory effects through suppression of NF-${\kappa}B$ and MAPK activation. These findings suggest that unripe RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• 대한핵의학회지
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• 제16권2호
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• pp.63-70
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• 1982

To evaluate the diagnostic usefulness and significance of quantitative sacroiliac joint scintigraphy in the assessment of sacroiliitis, we measured Sacroiliac Joint/Sacrum Uptake Ratio(SIS Ratio) by region of interest(ROI) method using $^{99m}Tc-methylene$ diphosphonate. The observed results were as follows: 1. Using ROI method, the SIS ratios for the control group of 65 persons were $1.05{\pm}0.08$(left) and $1.06{\pm}0.07$(right) which were narrower in range than those of slice method $(mean{\pm}S.D.)$. 2. The effects of age, gender and laterality on SIS ratio were not significant. 3. In left side, one of 6 patients with rheumatoid arthritis had SIS ratio in excess of 2 standard deviation of normal control group, and remainder had SIS ratios within normal limit. In right side, 3 patients had SIS ratios in excess of 2 standard deviation of normal control group, and remainder, within normal limit. 4. In both sacroiliac joint, 2 of 3 patients having sacroiliitis clinically with Reiter's syndrome whose pelvis A-P X-ray findings showed normal had high SIS ratios (left/right; 1.31/1.69, 1.90/1.80), but SIS ratio of one patient who had no evidence of sacroiliitis clinically was within normal limit. 5. In 6 patients with ankylosing spondylitis in both sacroiliac joints, 4 whose pelvis A-P Xray findings showed severe sclerotic change of sacroiliac joints had SIS ratio within normal limit or below that of normal control group, and SIS ratios of 2 patients whose pelvis A-P X-ray findings showed were increased. 6. 4 of 5 patients with low back pain of which cause could not be evaluated clinically and radiologically had SIS ratios in excess of that of normal control group. It would be concluded that quantitative sacroiliac joint scintigraphy is useful and sensitive screening method in the diagnosis as well as in the assessment clinical activity of sacroiliitis.

• 동의생리병리학회지
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• 제27권4호
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• pp.431-436
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• 2013

Bone homeostasis is maintained by co-ordination of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between osteoclasts and osteoblasts leads to many bone diseases such as osteoporosis, rheumatoid arthritis. Taxillus chinensis is a herb that has been widely used to improve bone health. However, the effect and mechanism of Taxillus chinensis extract on osteoclast differentiation and bone resportion has been unknown. Thus, We investigated the effect of Taxillus chinensis on expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation and bone resorption. Also, the action of Taxillus chinensis on mechanisms relating to osteoclast differentiation was studied. In this results, we identified that Taxillus chinensis significantly inhibited RANKL-induced osteoclast differentiation and bone resportion. Moreover, Taxillus chinensis was suppressed the activation of NF-${\kappa}B$ in bone marrow macrophage treated RANKL and M-CSF. Taxillus chinensis was down-regulated the mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP). The cell adhesion-related molecules such as integrin ${\alpha}v$ and integrin ${\beta}3$, and the filamentous actin (F-actin) rings of mature osteoclasts-related molecules such as dendritic cell-specific transmembrane preotein (DC-STAMP) and cathepsin K are also suppressed. Taken together, these results indicated that Taxillus chinensis will be a good candidate to treat osteoclast-mediated bone diseases.

• 동의생리병리학회지
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• 제27권6호
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• pp.782-788
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• 2013

Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae), colloquially known "Gujulcho" in Korea, has been used in traditional medicine for the treatment of various diseases, including cough, common cold, bladder-related disorders, gastroenteric disorders, hypertension, and inflammatory diseases, such as pneumonia, bronchitis, pharyngitis, and rheumatoid arthritis (RA) However, the effect of Chrysanthemum zawadskii var. latilobum on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of Chrysanthemum zawadskii var. latilobum extract (CZE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. CZE were not cytotoxic up to 100 ${\mu}g/ml$ concentration in the MCF-7 cell line. CZE decreased MMP-9 expression. TPA substantially increased NF-${\kappa}B$ DNA binding activity. Pre-treatment with CZE inhibited TPA-stimulated NF-${\kappa}B$ binding activity and NF-${\kappa}B$ related protein expression. To identify invasion ability of MCF-7 cells decreased by CZE, we used martrigel invasion assay. As a result, it is significantly decreased cell invasion. These results indicate that CZE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. Chrysanthemum zawadskii var. latilobum may have potential value in restricting breast cancer metastasis.

• 한국산학기술학회논문지
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• 제21권8호
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• pp.455-467
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• 2020

본 연구는 국내의 만성적인 신체질환을 가진 환자를 대상으로 임파워먼트 중재 연구 특성 및 효과를 조사하기 위해 체계적 문헌고찰을 수행하였다. PICOT-SD (Participants, Intervention, Comparison, Outcomes, Timing of outcome measurement, Setting, Study design) 전략이 적용되었다. 2000년 1월부터 2020년 4월에 발표된 총 19편의 논문을 선택하였다. 연구 대상자는 류마티스관절염 환자, 혈액투석 환자, 뇌졸중 환자, 당뇨병 환자, 만성폐질환자, 고혈압 환자, 암환자, 만성신부전 환자, 신장이식 환자 등이었다. 17편의 문헌에서 개념적 기틀이 제시되었다. 임파워먼트 전략은 참여, 대화, 경험 지지, 상호작용, 지지, 문제해결 등이었다. 자기관리(n=13), 임파워먼트(n=10), 자기효능감(n=7), 우울(n=5)이 많이 측정되었다. 대상자의 자기관리, 임파워먼트, 자기효능감을 측정한 문헌의 60% 이상에서 유의한 개선이 보고되었다. 본 연구에서의 고찰 결과, 임파워먼트 중재 연구는 만성적인 신체질환을 가진 환자의 건강 증진에 기여할 수 있는 효과적인 중재라고 생각된다. 추후 다양한 변수의 효과를 검증하는 임파워먼트 중재 프로그램을 개발할 필요가 있다.