• IMMUNE NETWORK
• /
• 제3권1호
• /
• pp.29-37
• /
• 2003

Background: CC chemokine receptor (CCR) 7 and cognate CCR7 ligands, CCL21 (formerly secondary lymphoid tissue chemokine [SLC]) and CCL19 (formerly Epstein-Barr virus-induced molecule 1 ligand chemokine [ELC]), were known to establish microenvironment for the initiation of immune responses in secondary lymphoid tissue. As described previously, coadministration of DNA vaccine with CCR7 ligand-encoding plasmid DNA elicited enhanced humoral and cellular immunity via increasing the number of dendritic cells (DC) in secondary lymphoid tissue. The author hypothesized here that CCR7 ligand DNA could effectively expand memory CD4+ T cells to protect from viral infection likely via increasing DC number. Methods: To evaluate the effect of CCR7 ligand DNA on the expansion of memory CD4+ T cells, DO11.10.BALB/c transgenic (Tg)-mice, which have highly frequent ovalbumin $(OVA)_{323-339}$ peptide-specific CD4+ T cells, were used. Tg-mice were previously injected with CCR7 ligand DNA, then immunized with $OVA_{323-339}$ peptide plus complete Freund's adjuvant. Subsequently, memory CD4+ T cells in peripheral blood lymphocytes (PBL) were analyzed by FACS analysis for memory phenotype ($CD44^{high}$ and CD62 $L^{low}$) at memory stage. Memory CD4+ T cells recruited into inflammatory site induced with OVA-expressing virus were also analyzed. Finally, the protective efficacy against viral infection was evaluated. Results: CCR7 ligand DNA-treated Tg-mice showed more expanded $CD44^{high}$ memory CD4+ T cells in PBL than control vector-treated animals. The increased number of memory CD4+ T cells recruited into inflammatory site was also observed in CCR7 ligand DNA-treated Tg-mice. Such effectively expanded memory CD4+ T cell population increased the protective immunity against virulent viral infection. Conclusion: These results document that CCR7 and its cognate ligands play an important role in intracellular infection through establishing optimal memory T cell. Moreover, CCR7 ligand could be useful as modulator in DNA vaccination against viral infection as well as cancer.

• 생명과학회지
• /
• 제13권4호
• /
• pp.541-550
• /
• 2003

본 실험에서는 C형 간염바이러스 (HCV)의 외피 단백질인 E2 당단백질에 결합하는 세포단백질들을 클로닝하기 위해 간세포 cDNA를 phage 표면에 발현시킨 phage library를 제작하였고, 12-mer peptide library와 함께 E2 단백질에 대해 panning을 실시하였다. 검색결과 세포내 신호전달과 cytoskeleton 구성에 관여하는 tensin, membrane protein band 4.1 등 세포질내 단백질과 CCR7, CKR-L2, insulin-like growth factor-1 receptor 등 세포막 단백질 등이 확인되었다. 이들 단백질들을 발현하는 phage들은 수용성 E2단백질을 이용한 결합중화반응 결과 E2 단백질에 특이적으로 결합함이 확인되었다. 사람 T 세포에서 주로 발현되는 CCR7 유전자를 PHA로 활성화된 사람 T 세포의 total RNA를 이용하여 증폭하고 클로닝하였다. 293T 세포에 transfection시켜 단백질 발현양상을 flow cytometer로 분석하여 70% 이상의 세포들이 CCR7을 발현하고 있음을 관찰하였다. 수용성 E2 단백질을 CCR7이 transfection된 세포와 mock transfection된 대조군 세포에 각각 반응시킨 결과 dose-dependent 양상으로 CCR7에 결합하였다.

• 통합자연과학논문집
• /
• 제6권3호
• /
• pp.163-169
• /
• 2013

The chemokine receptor CCR1 a GPCR super family protein contains seven transmembrane domains. It plays an important role in rheumatoid arthritis, organ transplant rejection, Alzheimer's disease and also causes inflammation. Because of its role in disease processes, antagonism of CCR1 became an attractive therapeutic target. In the current study, we have taken a novel series of recently reported CCR1 antagonist of 1-(4-Phenylpiperazin-1-yl_-2-(1H-Pyrazol-1-yl) ethanone derivatives and performed a HQSAR analysis. The model was developed with Atom (A) and bond (B) parameters and with different set of atom counts to improve the model. The results of HQSAR showed good predictive ability in terms of $r^2$ (0.904) and $q^2$ (0.590) with 0.710 as standard error of prediction and 0.344 as standard error of estimate. The contribution map depicted the atom contribution in inhibitory effect. Compound-14 which was reported to be a highly active compound showed positive atom contribution in three R groups ($R^3$. $R^{5a}$ and $R^{2b}$) in inhibitory effect, which could be the reason why this compound is highly active compound whereas, the lowest active compound-6 showed negative contribution to inhibitory effect.

• Journal of Ginseng Research
• /
• 제32권3호
• /
• pp.232-237
• /
• 2008

Cinnamoyl-CoA reductase (CCR, EC 1.2.1.44) catalyses the reduction of cinnamic acid CoA esters into their corresponding aldehydes, the first step of the phenylpropanoid pathway specially dedicated to monolignol biosynthesis. A cDNA clones encoding CCR have been isolated from Panax ginseng C.A. Meyer and its expression was investigated in response to abiotic stresses. The cDNA, designated PgCCR which is 865 nucleotides long and has an open reading frame of 590 bp with a deduced amino acid sequence of 176 residues. The PgCCR encoded protein possesses substantial homology with CCRs isolated and cloned from other sources; the highest identity (51.8%) was observed with CCR from Tomato (Lycopersicon esculentum). Under various stress conditions, expression patterns of the PgCCR were highly induced in adventitious and hairy roots by several abiotic stresses. These results indicated that PgCCR plays protective role against diverse environmental stresses.

• 대한한방소아과학회지
• /
• 제24권1호
• /
• pp.9-35
• /
• 2010

Objectives The purpose of this study is to investigate the effect of SPDJTK(SoPungDoJeokTangKami) and concurrent administration of AJ(Atopy cream, Jawoongo)+SPDJTK on atopic dermatitis-like skin lesions by using in NC/Nga atopic dermatitis mouse induced by BMAC-induced mice. Methods Clinical skin score, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mice were evaluated. Moreover, the cytokine level, total cell number, Immunohistochemical staining and Histological features of axillary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue were used in NC/Nga mice. Results Orally administrated SPDJTK with concurrent administration of SPDJTK and AJ decreased the clinical skin score, total cell number of WBC, eosinophils in blood, serum total IgE & IgG1, IL-5, IL-13, IFN-$\gamma$. Also, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, CD3+CD69+, CD3+CCR3+, CCR3+, CD4+CXCR5+ in ALN, absolute cell number of CD3+CCR3+, CCR3+ in DLN, granulocytes in PBMCs, activation cell number of CD3+CD69+, CCR3+, total cell number of CD3+ T cell in dorsal skin tissue were significantly decreased. Furthermore, thickness of epidermis, infiltrated inflammatory immune cell and mast cell in dermis, amount of Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue, gene expression of IL-5, IL-13 mRNA in ALN, CD4+ Th cell in dorsal skin tissue and CCR3+ eosinophils in ALN were all significantly decreased. However, total number of DLN, absolute number of CD3e+ T cell and CD19+ B cell, absolute number of CD4+, number of Th cell in DLN and gene expression of foxp3 mRNA were significantly increased significantly. Conclusions Concurrent administration of SPDJTK and AJ on atopic dermatitis in NC/Nga atopic dermatitis mouse was very effective treatment for atopic dermatitis.

• The Korean Journal of Pain
• /
• 제21권3호
• /
• pp.187-196
• /
• 2008

Background: Upregulation of one type of the pro-inflammatory chemokine (CCL2) and its receptor (CCR2) following peripheral nerve injury contributes to the induction of neuropathic pain. Here, we examined whether another type of chemokine (CCL3) is involved in neuropathic pain. Methods: We measured changes in mechanical and thermal sensitivity in the hind paws of naïve rats or rats with an L5 spinal nerve ligation (SNL) after intra-plantar injection of CCL3 or met-RANTES, an antagonist of the CCL3 receptor, CCR1. We also measured CCL3 levels in the sciatic nerve and the hind paw skin as well as CCR1 expression in dorsal root ganglion (DRG) cells from the lumbar spinal segments. Results: Intra-plantar injection of CCL3 into the hind paw of naive rats mimicked L5 SNL-produced hyperalgesia. Intra-plantar injection of met-RANTES into the hind paw of rats with L5 SNL attenuated hyperalgesia. L5 SNL increased CCL3 levels in the sciatic nerve and the hind paw skin on the affected side. The number of CCR1-positive DRG cells in the lumbar segments was not changed following L5 SNL. Conclusions: Partial peripheral nerve injury increases local CCL3 levels along the degenerating axons during Wallerian degeneration. This CCL3 binds to its receptor, CCR1, located on adjacent uninjured afferents, presumably nociceptors, to induce hyperalgesia in the neuropathic pain state.

• The Journal of Korean Physical Therapy
• /
• 제22권3호
• /
• pp.99-105
• /
• 2010

Purpose: The purpose of this study was to evaluate the development of pain behavior and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 at above and below the level of hemisection of the spinal cord in a rat model. Methods: Spinal cords of adult female Sprague-Dawley rats (n= 16, 200~250 g, 6~8 weeks old) were hemisected at T13 on the right side to develop the spinal hemisection injury model. We compared behavioral responses of the hemisection and of a sham surgery group. Behavioral tests for motor function (by the BBB locomotor scale), and for pain response for mechanical and cold allodynia were assessed postoperatively (PO) for 21 days. Expression of mRNA for chemokines and their receptors (CCL2/CCR2 and CX3CL1/CX3CR1) below and above the level of the spinal cord dissection were examined by RT-PCR. Results: We observed gradual motor improvement and the development of mechanical and cold allodynia on the ipsilateral hindpaw after spinal hemisection injury. We also found upregulation of mRNA expression of CCL2/CCR2 both above and below the level of spinal cord dissection but CX3CL1/CX3CR1 mRNA expression. Conclusion: Upregulation of CCL2/CCR2 is associated with neuropathic pain after spinal hemisection injury. CCL2/CCR2 may play an important role in the development of neuropathic pain after SCI as well as of peripheral neuropathic pain. These findings may improve understanding of the pathophysiological mechanism of neuropathic pain after SCI.

• 한국콘텐츠학회논문지
• /
• 제19권8호
• /
• pp.151-158
• /
• 2019

국내 전기 전자 산업이 보유하고 있는 높은 기술력은 국외 시장에서도 인정받고 있지만 현재 주변국과의 기술경쟁 등이 갈수록 심화되어져 가고 있는 상황이다. 따라서 이들 기업들이 경쟁우위를 차지하기 위해서는 무엇보다 운영상의 비효율성을 재정비하여 효율적인 생산 활동을 실시하여야한다. 이에 본 논문에서는 DEA 기업을 통해 국내 고성장 전기 전자사업의 경영효율성을 분석하며 비효율적인 기업의 투사값을 제시하며 벤치마킹의 대상이 될 수 있는 기업들의 참조집합을 확인하고자 한다. 이를 위해 총 20개 고성장 전기 전자기업들의 CCR와 BCC모형의 효율성과 규모수익성(RTS)을 분석하였다. 분석결과 BCC 효율성이 1인 기업은 총 12개, CCR 효율성이 1인 기업은 총 4개 기업으로 나타났다. 그리고 BCC, CCR 효율성이 모두 1인 기업은 총 4개 기업이었다. 또한 기업의 규모수익성은 IRS가 11개 기업, CRS가 6개 기업 그리고 DRS가 3개 기업으로 분석되었으며 참조빈도 분석에서는 BCC모형에서는 4개 기업과 CCR 모형을 통해 4개 기업을 벤치마킹이 할 수 있는 기업으로 제시하였다. 이러한 결과는 동종 산업의 후발 기업들에게 기업의 운영환경을 개선할 수 있는 유용한 정보가 될 것이다.

• Journal of Yeungnam Medical Science
• /
• 제41권2호
• /
• pp.103-112
• /
• 2024

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8⁺ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

• Plant Resources
• /
• 제8권3호
• /
• pp.181-187
• /
• 2005

A cinnamoyl CoA reductase (CCR) cDNA (ClCCR) was isolated from tabroot mRNAs of Codonopsis lanceolata by cDNA library construction, and its expression was investigated in relation to abiotic stresses. The ClCCR is 1008 bp in length with an open reading frame (ORF) of 336 amino acids. The deduced amino acid sequence was showed high similarity with cinnamoyl-CoA reductases of P. tremuloides (AAF43141) 87%, F.${\times}$aranassa (AAP46143) 83%, L. album (CAD29427) 80%, E. gunnii (CAA66063) 72%, S. tuberosum (AAN71761) 83%. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was revealed that the ClCCR expression was regulated by abiotic stresses.