• Journal of Periodontal and Implant Science
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• 제34권3호
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• pp.607-622
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• 2004

Recently epidemiologic studies have indicated that the patients with periodontitis may have increased risk of ischemic cardiovascular events, and have suggested the important roles of blood cytokines and acute reactant proteins in the systemic infection and inflammatory response. Periodontitis and coronary heart disease (CHD) may share the common risk factors and the genetic mechanism associated with interleukin(IL)-1A, B and RA genotype may be involved in the production of IL-1. This study was aimed to investigate the relationship between angiographically defined CHD and periodontitis as chronic Gram-negative bacterial infection and to determine whether the IL-1 gene polymorphism is associated in both diseases. Patients under the age of 60 who had undergone diagnostic coronary angiography were enrolled in this study. Subjects were classified as positive CHD (+CHD, n=37) with coronary artery stenosis more than 50% in at least one of major epicardial arteries, and negative CHD (-CHD, n=30) without significant stenosis. After recording the number of missing teeth, periodontal disease severity was measured by means of plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and radiographic bone loss around all remaining teeth. Gingival crevicular fluid (GCF) was collected from the 4 deepest periodontal pockets and assessed for cytokine ($IL-1{\beta}$, IL-6, IL-1ra, tumor necrosis $factor-{\alpha}$, and prostaglandin $E_2$). Additionally, blood CHD markers, lipid profile, and blood cytokines were analyzed. IL-1 gene cluster genotyping was performed by polymerase chain reaction and enzyme restriction using genomic DNA from buccal swab, and allele 2 frequencies of IL-1A(+4845), IL-1B(+3954), IL-B(-511), and IL-1RA(intron 2) were compared between groups. Even though there was no significant difference in the periodontal parameters between 2 groups, GCF level of $PGE_2$ was significantly higher in the +CHD group(p<0.05). Correlation analysis showed the positive relationship among PD, CAL and coronary artery stenosis(%) and blood $PGE_2$. There was also significant positive relationship between the periodontal parameters (PI, PD, CAL) and the blood CHD markers (leukocyte count, C-reactive protein, and lactic dehyrogenase). IL-1 gene genotyping showed that IL-1A(+3954) allele 2 frequency was significantly higher in the +CHD group compared with the -CHD group (15% vs. 3.3%, OR 5.118,p=0.043). These results suggested that periodontal inflammation is related to systemic blood cytokine and CHD markers, and contributes to cardiovascular disease via systemic inflammatory reaction. IL-1 gene polymorphism might have an influence on periodontal and coronary heart diseases in Korean patients.

• 한국응용과학기술학회지
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• 제35권2호
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• pp.509-518
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• 2018

이 연구의 목적은 신체활동이 마이오카인 발현에 미치는 영향을 보고자 문헌고찰을 하였다. 신체적인 활동은 제2형 당뇨, 심혈관질환, 대장암, 치매 및 우울증과 같은 질환을 예방하는 역할을 하고 있다. 그리고 마이오카인(myokine)은 운동 훈련에 의해 분비되는 호르몬으로 뇌성장이나 알츠하이머 같은 질환 예방에 도움을 준다. 운동수행과정에서 수축하는 근육으로부터 분비되는 항염증 마이오카인의 생성과 대사 조절에 필요한 분비 활성화가 건강증진에 중요한 요인으로 보고 있다. 인체 골격근에서 분비되는 마이오카인 가운데 IL-4, IL-6, IL-7, IL-8, IL-15 등은 근육비대(hypertrophy)와 세포(myogenesis) 및 혈관생성(angiogenesis) 등의 조절에 관여한다. IL-6는 AMPK 활성화로 인한 대사중 지방 산화를 촉진시키는 작용을 하고, IL-1Ra, IL-10 과 sTNF-R 는 염증성 싸이토카인 $TNF-{\alpha}$의 분비를 억제한다. IL-15는 저항 운동시 근수축을 통한 발현량이 증가하어 근육 성장의 중요 합성요인으로 작용한다. 한편 IL-7 및 IL-8도 신호 전달 수용체 C-X-C를 통해 혈관신생을 촉진시킨다.

• IMMUNE NETWORK
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• 제4권3호
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• pp.190-197
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• 2004

Background: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic synovial inflammation which leads to joint destruction. Gene therapy of RA targets the players of inflammation or articular destruction. However, viral vectors have safety problems and side effects, while non-viral vectors suffer from inefficient gene transfer and fast loss of gene expression. To overcome the limits of non-vial vectors, an EBV-based plasmid which is known to exert prolonged high level gene expression can be used. Methods: pEBVGFP, pEBVIL-10, and pEBVvIL-10 were constructed by cloning GFP, IL-10, and vIL-10 genes into an EBV-based plasmid, respectively. The pGFP was used as a control plasmid. Each constructs were lipofected into HIG-82 rabbit synoviocytes. The expression of GFP was monitored by FACS and confocal microscopy. IL-10 and vIL-10 expressions were measured by ELISA. Results: GFP expression 2 days after transfection was achieved in 33.2% of cells. GFP-expressing cells transfected with pGFP decreased rapidly from 4 days after transfection and disappeared completely by 11 days. Cells transfected with pEBVGFP began to decrease slowly from 4 days. But GFP expression was detected for over 35 days. In addition, HIG-82 cells transfected with pEBVIL-10 ($44.6{\pm}1.5ng/ml$) or pEBVvIL-10 ($51.0{\pm}5.7ng/ml$) secreted these cytokines at high levels. High level cytokine production by hygromycin selection was maintained at least for up to 26 days after transfection. Conclusion: These results suggest that the EBV-based plasmid has a potential to improve non-viral gene transfer system and may be applicable to treat RA without the drawbacks of viral vectors.

• Journal of Acupuncture Research
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• 제25권4호
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• pp.81-94
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• 2008

Rheumatoid arthritis(RA) is a general, chronic, inflammatory and auto-immune disease and it can lead to joint edema, pain, stiffness which are caused by an inflammation in synovium covering our joints. Ulmus davidiana Planchon is a traditional herb used for the treatment on various inflammations, gastrointestinal trouble, ENT(ear, nose, and throat) disease, edema, cancer etc. and it works effectively on arthritis as well. In these study to search for the treatment efficacy of Ulmus davidiana Planchon in RA, I measure manifestation of cytokine gene in synoviocyte treated with Ulmus davidiana Planchon herbal acupuncture and in EL-4 cell, manifestation of cytokine gene cell related to T-cell. And after Ulmus davidiana Planchon herbal acupuncture treatment in Collagen induced arthritis(CIA) which has been known by a general model of RA, DBA mice, I observed foot thickness, general shape of synovium, early cytokine induce CIA and, generation and mutation of cytokine related to the control of T-cell specialization. It comes to conclusion as belows. 1. In synovium treated with Ulmus davidiana Planchon herbal acupuncture, there was the decrease in MIF mRNA does-dependently. Incase of CIA mice treated with Ulmus davidiana Planchon herbal acupuncture, there were the decrease in the damage in synovium and generation of the MIF which is related to induction of the early RA cytokine and IL-6 proinflammatory cytokine. 2. In case of EL-4 treated with Ulmus davidiana Planchon herbal acupuncture, there were decrease in the manifestation of the IL-2 mRNA, but the increase in the manifestation of the IL-4 does-dependently. 3. In the synovium of CIA mice treated with Ulmus davidiana Planchon herbal acupuncture, there were the decrease in generation of IL-2, IL-12 and CD-28, but the increase in generation of IL-4. These result suggest that Ulmus davidiana Planchon can block the process of the early RA by Inhibiting MIF activation, and mitigate Rheumatoid Arthritis by controlling Tcell specialization.

• 대한한방소아과학회지
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• 제30권4호
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• pp.29-59
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• 2016

Objectives PRAL (Prunus armeniaca Linne Var) has been known to suppress allergic reaction. However, the cellular target and its mechanism of action were unclear. This study was designed to investigate the effect of PRAL on RBL-2H3 mast cell, which is PMA-Ionomycin-induced activated in vitro and the effect of PRAL on the MNC/Nga mice that are DNCB-induced activated in vivo. Methods In this study, IL-4, IL-13 production were examined by ELISA analysis; IL-4, IL-13, IL-31, IL-31Ra, $TNF-{\alpha}$ and GM-CSF mRNA expression were examined by Real-time PCR; manifestations of AP-1 and MAPKs transcription factors were examined by western blotting in vitro. Then skin rashes have been evaluated and verified the distribution of mast cells by H&E and toluidine blue. Also, WBC, eosinophil and neutrophil, IgE level in serum, $IFN-{\gamma}$, IL-4, IL-5 in the splenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$, $CD3^+CD69^+$ in the Axillary Lymph Node (ALN), PBMCs and dorsal skin and IL-5, IL-13, IL-31, IL-31Ra in the dorsal skin by Real-time PCR were all evaluated from the NC/BNga mice. Results As a result of this study, the mRNA expression of IL-4, IL-13, IL-31, IL-31Ra and $TNF-{\alpha}$ and IL-4, IL-13 production, shown in ELISA analysis, were suppressed by PRAL. Results from the western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including AP-1 and p-JNK, p-ERK. Histological examination showed that infiltration levels of immune cells in the skin of the AD-induced NC/Nga mice were improved by PRAL orally adminstration. Orally- administered PRAL group also showred decreased level of IgE in the serum. This group has shown decreased the level of IL-4, IL-5, but shown elevated $IFN-{\gamma}$ level in the splenocyte culture supernatant. The same group also has shown decreased cell numbers of $CD4^+$, $CD8^+$, $CD3^+CD69^+$ in the ALN, and $CD4^+$, $Gr-1^+CD11b^+$ in the dorsal skin. PRAL oral adminstration increased cell numbers of $CD4^+$, but decreased cell numbers of $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$ in the PBMCs. Conclusions Obtained results suggest that PRAL can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis (AD) induced in the NC/Nga mice. This may play an important role in recovering AD symptoms and suppressing pruritus.

• Genomics & Informatics
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• 제9권3호
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• pp.114-120
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• 2011

Chronic inflammation has been implicated as one of the important etiological factors in insulin resistance and type 2 diabetes mellitus (T2DM). To investigate the role of anti-inflammatory cytokines in the development of T2DM, we conducted a case-control study to assess the association between IL4/IL4R polymorphisms and disease risk. We firstly identified single nucleotide poly-morphisms (SNP) at IL4 and IL4RA loci by sequencing the loci in Korean participants. Case-control studies were conducted by genotyping the SNPs in 474 T2DM cases and 470 non-diabetic controls recruited from community-based cohorts. Replication of the associated signals was performed in 1,216 cases and 1,352 controls. We assessed effect of IL4 -IL4RA interaction on T2DM using logistic regression method. The functional relevance of the SNP associated with disease risk was determined using a reporter expression assay. We identified a strong association between the IL4 promoter variant rs2243250 and T2DM risk (OR=0.77; 95% CI, 0.67~0.88; p=$1.65{\times}10^{－4}$ in the meta-analysis). The reporter gene expression assay demonstrated that the presence of rs2243250 might affect the gene expression level with ~1.5-fold allele difference. Our findings contribute to the identification of IL4 as a T2D susceptibility locus, further supporting the role of anti-inflammatory cytokines in T2DM disease development.

• Macromolecular Research
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• 제14권1호
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• pp.66-72
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• 2006

The purpose of this study is to develop novel nanoparticles based on polyion complex formation between low molecular weight water-soluble chitosan (LMWSC) and all-trans retinoic acid (atRA). LMWSC nanoparticles encapsulating atRA based on polyion complex were prepared by mixing of atRA into LMWSC aqueous solution using ultrasonication. In FTIR spectra, the carbonyl group of atRA at 1690 $cm^{-1}$ disappeared or decreased when ion complexes were formed between LMWSC and atRA. In ${1}^H$ NMR spectra, specific peaks of atRA disappeared when atRA-encapsulated LMWSC (RAC) nanoparticles were reconstituted into $D_{2}O$ while specific peaks both of atRA and LMWSC appeared in $D_{2}O$/DMSO (1/3, v/v) mixture. XRD patterns also showed that the crystal peaks of atRA were disappeared by encapsulation into LMWSC nanoparticles. LMWSC nanoparticles encapsulating atRA have spherical shapes with particle size below 200 nm. The mechanism of encapsulation of atRA into LMWSC nanoparticles was thought to be an ion complex formation between LMWSC and atRA. LMWSC nanoparticles showed high atRA loading efficiency over 90$\%$ (w/w). AtRA was continuously released from nanoparticles over 10 days. In in vitro cell cytotoxicity test, free atRA showed higher cytotoxic effect against CT 26 colon carcinoma cell line on 1 day. However, RAC nanoparticles showed similar cytotoxicity against CT 26 cells on 2 day. These results suggest the potential for the introduction of LMWSC nanoparticles into various biomedical fields such as drug delivery.

• 대한피부과학회지
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• 제56권10호
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• pp.609-613
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• 2018

Background: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. Objective: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). Methods: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. Results: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. Conclusion: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.

• 센서학회지
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• 제33권2호
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• pp.70-77
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• 2024

In this study, a fluorescent ethanol sensor is developed to determine the ethanol concentration in the liquid phase. The sensor is developed using a complex of resazurin (RA)/resorufin (RO) and a hydrotalcite (HT) catalyst in a sol-gel matrix of methyltrimethoxysilane (MTMS) to produce a fluorescent ethanol-sensing membrane (RA/RO^*HT membrane). The operation mechanism of the RA/RO^*HT membrane is based on (i) the oxidation of ethanol to acetaldehyde and (ii) the reduction of RA to RO, through electron flows followed by EtOH ↔ HT ↔ RA/RO ↔ EtOH interactions. These possible redox reactions can lead to an increased fluorescence intensity of the RA/RO^*HT membrane as the ethanol concentration increases. The RA/RO^*HT membrane shows a linear detection range of 1-20 vol.% EtOH with limit of detection (LOD) of 0.178%. Additionally, the RA/RO^*HT membrane has high sensitivity and accuracy for determining the alcohol content in several Korean alcoholic beverages.

• Imaging Science in Dentistry
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• 제35권4호
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• pp.191-198
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• 2005

Purpose: To characterize the effects of 2-deoxy-D-glucose (2DG) and quercetin (QCT) on cytokine secretion of IL-6, $TGF-\beta$ and gene expression of Col I in irradiated MC3T3-E1 cells Materials and Methods: The MC3T3-El cells were cultured in an a-MEM supplemented with 5mM 2DG or 10mM QCT and then the cells were incubated 12h before irradiation with 2, 4, 6, and 8Gy X-ray using a linear accelerator delivered at a dose rate of 1.5Gy/min. Level of IL-6 and $TGF-\beta$ was determined by ELISA. Also expression of Col I was examined by RT-PCR. Results: In accordance with the radiation dose, the amount of $TGF-\beta$ was not different in RA + QCT, but it showed a peak value in control and RA + 2DG at 4Gy on the 3rd day. However, all groups showed a decreasing tendency dose-dependently in RA+QCT on the 7th day (p<0.01). In accordance with the radiation dose, the amount of IL-6 increased dose-dependently in all groups on the 3rd day. On the 7th and 21st day, all groups showed peak values at 4Gy. RA+QCT showed a slightly increased amount of IL-6 at 2Gy, but it showed a slightly decreased amount at 4, 6, and 8Gy. In accordance with the period of culture after irradiation, the expression of Col I increased dose-dependently in RA+QCT. Conclusion: The result showed that QCT acted as radiosensitizer in the secretion of $TGF-\beta$ and gene expression of Col I during differentiation in irradiated MC3T3-E1 cells at the cellular level.