• Tuberculosis and Respiratory Diseases
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• 제59권5호
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• pp.517-521
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• 2005

배 경 : 흉수에서 기질 금속단백분해효소(MMP)와 금속단백분해효소 조직억제제(TIMP)는 감염과 면역질환의 병인에 중요한 역할을 한다. 저자들은 삼출성 흉수에서 MMP-1과 TIMP-1의 발현에 대한 측정을 하였다. 방 법 : 결핵성 흉막염 33예, 악성흉수 17예, 심부전 또는 간경화 흉수환자 5예의 흉막천자액에서 세포분석, 생화학적 분석을 하였고, 효소면역측정방법으로 MMP-1과 TIMP-1(Biotrack$^{TM}$, Amersharm Pharmacia Biotech, Freiburg, FRG)를 측정하였다. 결 과 : 흉수 MMP-1은 결핵성 흉수(n=33, $12.1{\pm}8.8ng/mL$)가 악성 흉수(n=17, $4.8{\pm}4.0ng/mL$)나 누출액(n=5, $2.6{\pm}1.5ng/mL$)보다 높았다(p=0.002). 흉수 TIMP-1은 결핵성 흉수(n=23, $110.9{\pm}38.2{\mu}g/mL$)가 누출성 흉수(n=5, $53.7{\pm}21.8{\mu}g/mL$)보다 높았고(p=0.004), 악성 흉수(n=17, $90.2{\pm}39.8{\mu}g/mL$)도 누출성 흉수보다 높았으나(p=0.039), 결핵성 흉수와 악성 흉수는 유의한 차이가 없었다(p=0.132). 결 론 : 흉수 MMP-1, TIMP-1는 결핵성 흉막염에서 심부전이나 간경화 흉수보다 높았다.

• Journal of Periodontal and Implant Science
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• 제40권1호
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• pp.33-38
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• 2010

Purpose: The purpose of this study was to observe and quantify the expression of interleukin-4 (IL-4), interferon-$\gamma$ (IFN-$\gamma$), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the gingival tissue of patients with type 2 diabetes mellitus (DM) and healthy adults with chronic periodontitis. Methods: Twelve patients with type 2 DM and chronic periodontitis (Group 3), twelve patients with chronic periodontitis (Group 2), and twelve healthy individuals (Group 1) were included in the study. Clinical criteria of gingival (sulcus bleeding index value, probing depths) and radiographic evidences of bone resorption were divided into three groups. The concentrations of cytokines were determined by a western blot analysis and compared using one-way ANOVA followed by Tukey's test. Results: The expression levels of IFN-$\gamma$ and TIMP-2 showed an increasing tendency in Groups 2 and 3 when compared to Group 1. On the other hand, the expression of IL-4 was highest in Group 1. Conclusions: The findings suggest that IFN-$\gamma$ and TIMP-2 may be involved in the periodontal inflammation associated with type 2 DM. IL-4 may be involved in the retrogression of the periodontal inflammation associated with type 2 DM.

• Journal of Periodontal and Implant Science
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• 제41권3호
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• pp.109-116
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• 2011

Purpose: The purpose of this study was to compare and quantify the expression of C-reactive protein (CRP), matrix metalloproteinase (MMP)-14, and tissue inhibitor of metalioproteinases (TIMP)-2 in gingival tissues of patients with chronic periodontitis accompanied with inflammatory reaction related to alveolar bone resorption with or without type 2 diabetes mellitus (DM). Methods: Twelve patients with type 2 DM and chronic periodontitis (group 3), twelve patients with chronic periodontitis (group 2), and twelve healthy individuals (group 1) were included in the study. Gingival tissue biopsies were collected from each patient and from healthy individuals at the time of periodontal surgery (including surgical crown lengthening) or tooth extraction. The concentrations of cytokines were determined by a western blot analysis. Results: The expression levels of CRP and MMP-14 increased in group 2 and 3, and they were highest in group 3. The expressions of TIMP-2 also increased in group 2 and 3. Conclusions: This study demonstrated that the expression levels of CRP, MMP-14, and TIMP-2 might be inflammatory markers in periodontal inflamed tissue. It can be assumed that CRP, MMP-14, and TIMP-2 may be partly involved in the progression of periodontal inflammation associated to type 2 DM.

• Tuberculosis and Respiratory Diseases
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• 제53권4호
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• pp.420-430
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• 2002

연구배경 :임상적으로 만성 기관지염 환자의 호흡기 증상이 급격히 악화되는 것으로 정의되는 만성 기관지염의 급성악화는 기도의 폐쇄를 조장하여 만성 폐쇄성 폐질환으로의 진행을 촉진시키는 것으로 알려져 있다. 방 법 :만성 기관지염의 급성악화 환자 40명을 대상으로 하였으며 대상 환자를 무작위로 moxifloxacin군과 clarithromycin군으로 나누어 항생제를 경구투여 하였다.항생제를 복용 하기 전과 항생제를 7일간 복용한 후 각각 객담을 유도 처리하여 유도객담 상층액 내의 IL-8, SLPI, MMP-1, MMP-9, TIMP-1의 농도를 ELISA 방법으로 측정하였다. 결 과 : 항생제 투여에 의해 유도객담 내 TIMP-l의 농도와 TIMP-1/MMP-1의 분자량 비율이 유의하게 감소하였고 (p<0.05), 유도객담 내 SLPI의 농도는 유의하게 증가하였다(p<0.01) 급성악화 시 유도객담 내의 TIMP-1의 농도(p<0.01, r=0.751)와 TIMP-l/MMP-1의 분자량 비율(p<0.01, r=0.752)은 IL-8과 유의한 상관관계를 보이고 있었으며 항생제 치료로 호전이 된 이후에도 IL-8과의 상관관계는 계속 관찰되었다. 급성악화 시 유도객담 내 SLPI의 농도는 유도객담 내 TIMP-1(p<0.01, r=-0.496)과 TIMP-1/MMP-1(p<0.01, r=-0.456)의 분자량 비율 변화와 유약한 상관관계가 있었다. 그러나 유도객담 내 MMP-1, MMP-9의 농도 그리고 TIMP-l/MMP-9의 분자량 비율은 IL-8이나 SLPI의 농도와 유의한 상관관계가 없었다. 결 론 : 만성 기관지염의 급성 악화에 의해 TIMP와 MMPs의 불균형이 초래되며 TIMP가 상대적으로 많이 증가함으로써 기도 내 ECM이 축적되는데 적절한 항생제를 사용하지 않았을 때에는 이러한 기도벽의 재구성이 반복되어 기도의 폐쇄가 심해질 것으로 생각된다. TIMP와 MMPs의 불균형은 항생제 치료에 의하여 호전이 됨으로 적절한 항생제 치료는 만성 기관지염의 급성악화에 의한 비가역성 기도 폐쇄가 진행되는 것을 어느 정도 예방할 수 있을 것으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제46권6호
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• pp.548-553
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• 2003

목 적 : 뇌수막염에서 MMP-9은 뇌혈관 내피하 기질막을 분해하여 혈관-뇌장벽을 파괴하는데 주된 역할을 담당하며 TIMP-1은 MMP-9의 전효소와 복합체를 형성하여 MMP-9의 작용을 선택적으로 억제하는 인자로 알려져 있으나 이들의 상호작용은 아직 밝혀진 바가 별로 없다. 최근 세균성 뇌수막염 환자의 뇌척수액에서 MMP-9과 TIMP-1 측정에 대한 연구가 있었고, 특히 세균성 뇌수막염에서 신경학적 합병증의 예후인자와 관련하여 MMP-9의 역할에 대한 보고들이 있었으나 아직 무균성 뇌수막염 환자를 대상으로 한 보고는 별로 없었고 특히 국내에서 보고된 바는 없었다. 이에 저자들은 무균성 뇌수막염 환아의 혈액과 뇌척수액에서 MMP-9과 TIMP-1의 농도를 측정하여 대조군과 비교하고, MMP-9과 TIMP-1 및 다른 뇌수막염 관련인자들 사이의 상관관계를 비교 분석하고자 하였다. 방 법: 2002년 6월부터 7월까지 강북삼성병원 소아과 내원환자 중 발열과 뇌막자극증상을 보인 40명의 환아들을 대상으로 뇌척수액 검사를 시행하여, 무균성 뇌수막염 소견을 보인 25명을 뇌수막염군, 정상소견을 보인 14명을 대조군으로 하였다. 입원당일 혈액과 뇌척수액을 채취하여 혈액에서 백혈구수를 측정하고, 뇌척수액에서 백혈구수와, 당, 단백농도 및 뇌압을 측정하였다. 나머지 혈액 및 뇌척수액 검체는 실온에서 10분간 2,000g으로 원심분리하여 영하 70도에서 보관후 sandwich ELISA 방법을 이용하여 각각의 검체에서 일시에 MMP-9과 TIMP-1의 농도를 정량하였다. 결 과 : 뇌척수액 MMP-9과 TIMP-1 농도는 뇌수막염군에서 의미있게 증가되었고(P<0.05), 혈청 MMP-9과 TIMP-1 농도는 두 군간에 차이가 없었다. 뇌척수액 MMP-9과 TIMP-1은 서로 의미있는 양의 상관관계를 보였으며($r_s=0.42$, P<0.05), 뇌척수액 MMP-9/TIMP-1 비율은 대조군에 비해 무균성 뇌수막염군에서 의미있게 증가되었다(P<0.05). 뇌척수액 MMP-9과 TIMP-1은 뇌척수액 총백혈구수와 양의 상관관계를 보였다($r_s=0.43$, P<0.05, $r_s=0.48$, P<0.05). 뇌척수액 TIMP-1은 뇌척수액 단백 농도와 양의 상관관계를 보였다($r_s=0.43$, P<0.05). 결 론 : 무균성 뇌수막염 환아의 급성기 뇌척수액에서 MMP-9과 TIMP-1이 의미있는 증가를 보였고, 뇌척수액 TIMP-1은 정상군에서 상대적으로 높은 농도를 보이고 있어 MMP-9과 TIMP-1은 각각 뇌혈관장벽의 파괴와 유지에 관여한다고 생각된다.

• BMB Reports
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• 제32권1호
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• pp.60-66
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• 1999

Matrix metalloproteinase-2 (MMP-2; 72-kDa gelatinase; 72-kDa type IV collagenase; gelatinase A) plays an important role in normal physiological processes and in many pathologic processes such as arthritis and metastasis of cancer. Tissue inhibitor of metalloproteinases-2 (TIMP-2) binds to proMMP-2 or mature MMP-2 at a 1:1 ratio and inhibits the catalytic activity of MMP-2. We demonstrated that the baculovirus/insect cell system does not have TIMP-2 activity. The human proMMP-2 free of TIMP-2 was expressed in the expression system and purified by one-step affinity chromatography using gelatin-Sepharose. The free proMMP-2 was autoactivated to the mature MMP-2 and autodegraded into smaller molecular weight forms in the absence of external activator. The activation and autodegradation of the proMMP-2 was much more rapid in the presence of 4-aminophenylmercuric acetate (APMA). Addition of TIMP-2 inhibits both APMA-induced activation and autodegradation of the free proMMP-2. However, an increasing concentration of TIMP-2 more readily inhibited activation of the free proMMP-2 than autodegradation. These results demonstrate that TIMP-2 plays roles in inhibition of both activation and autodegradation of the free proMMP-2 in addition to inhibition of the catalytic activity of MMP-2.

• 약학회지
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• 제48권3호
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• pp.189-196
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• 2004

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) playa key role in tumor invasion and metastasis. As an inhibitor of MMP-2, TIMP-2 is known to block both the invasive and metastatic behavior of cancer cells, and decrease tumor growth activity. We performed this study to investigate the effects of TIMP-2 over-expression induced by retroviral mediated gene transfer in vitro and in vivo. The human colon cancer cell line SW480 was transfected with the retroviral vector encoding TIMP-2. The effects of TIMP-2 over-expression were analyzed by invasion assay and gelatinase activity test in colon cancer cells and tumorigencity in nude mice. In evaluation of the transfection efficiency of the retroviral vector encoding TIMP-2 in colon cancer cells, we confirmed up-regulation of TIMP-2 expression dependent on the time of cell culture. In addition, inhibition of MMP-2 expression in SW480/TIMP-2 was shown by gelatin zymography. In the in vitro invasion assay SW480/TIMP-2 inhibited the invasiveness on matrigel coated with collagen. To determine whether TIMP-2 can modulate in vivo tumorigenicity and metastasis, SW480/TIMP-2 cells were injected subcutaneously in nude mice. The tumor mass formation of SW480/TIMP-2 cells in nude mice was markedly decreased compared to nontransfected cancer cells. These results showed that colon cancer cells transfected with the retroviral vector encoding TIMP-2 inhibits the invasiveness in vitro and tumorigenicity in vivo.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권5호
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• pp.404-416
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• 2006

Purpose : This study was to clarify the changes in mandibular condyle after unilateral mandibular distraction osteogenesis throughout histological changes and expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). Materials & Methods : Intraoral distractors were placed via submandibular incision in 8 dogs. Two unoperated animals served as controls. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. Two animals were sacrificed on 7, 14, 28, and 56 days after completion of distraction, respectively. Ipsilateral condyles were harvested and processed for histological and immunohistochemical examinations. Results : The condyle cartilage is separated into four layers: fibrous layer, proliferative layer, hypertrophic layer, and calcified layer. At 7 days and 14 days after distraction, the condylar cartilage showed the decreased thickness of the articular cartilage and reduced cellularity. At 28 days after distraction, there was an increase in cellularity of fibrous, proliferative, and hypertrophic layer. However, it demonstrated reduced cellularity compared to the control. At 56 days of after distraction, the articular cartilage was an almost normal histologic structure. Positive Safranin-O staining, indicative of sulfated proteoglycans, was examined in the condylar cartilge of nonloaded control. At 7 days and 14 days after distraction, the sulfated proteoglycans is almost completely depleted from the noncalcified part of the condylar cartilage. At 28 days after distraction, there was an increase in Safranin-O staining intensity. However, the staining intensity of the experimental condyle was weaker than that of the control. At 56 days of after distraction, the condylar cartilage showed almost normal Safranin-O staining pattern. In control condyle, MMP-2 immunostaining was seen in fibrous, proliferative, and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in fibrous and proliferative layer. At 7 days and 14 days after distraction, strong MMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, MMP-2 immunostaining was seen in the fibrous and hypertrophic layer of condylar cartilage, however, their immunoactivity was reduced. At 56 days after distraction, MMP-2 immunoreactivity showed almost normal immunostaining pattern. In control condyle, TIMP-2 immunostaining was primarily seen in fibrous and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in proliferative layer. At 7 days after distraction, very weak TIMP-2 immunoreactivity appeared in fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 14 days after distraction, weak TIMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, TIMP-2 immunoreactivity was increased in the fibrous and hypertrophic layer of condylar cartilage. At 56 days after completion of distraction, TIMP-2 immunoreactivity showed almost normal immunostaining pattern. Conclusions : The results show that short-term outcome of physiologic distraction osteogenesis may lead to degenerative changes in the condylar cartilage. These alterations in the condylar cartilage may be considered as a pressure-related degeneration of the cartilage tissue. However, the long-term results suggest that the condylar cartilage display repair activity after mandibular distraction osteogenesis.

• Clinical and Experimental Pediatrics
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• 제58권11호
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• pp.415-420
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• 2015

Purpose: Bronchopulmonary dysplasia (BPD) is characterized by inflammation with proteolytic damage to the lung extracellular matrix. The results from previous studies are inconsistent regarding the role of proteinases and antiproteinases in the development of BPD. The aim of the present study was to investigate whether matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-1 levels in the serum of preterm infants at birth are related to the development of BPD. Methods: Serum was collected from 62 preterm infants at birth and analyzed for MMP-8, MMP-9, TIMP-2, and TIMP-1 by using enzyme-linked immunosorbent assay. MMPs and TIMPs were compared in BPD (n=24) and no BPD groups (n=38). Clinical predictors of BPD (sex, birth weight, gestational age, etc.) were assessed for both groups. The association between predictors and outcome, BPD, was assessed by using multivariate logistic regression. Results: Sex, birth weight, and mean gestational age were similar between the groups. BPD preterm infants had significantly lower TIMP-2 levels at birth compared with no BPD preterm infants ($138.1{\pm}23.0ng/mL$ vs. $171.8{\pm}44.1ng/mL$, P=0.027). No significant difference was observed in MMP-8, MMP-9, and TIMP-1 levels between the two groups. Multivariate logistic regression analysis indicated that the TIMP-2 levels were predictive of BPD after adjusting for sex, birth weight, gestational age, proteinuric preeclampsia, and intraventricular hemorrhage (${\beta}=-0.063$, P=0.041). Conclusion: Low TIMP-2 serum levels at birth may be associated with the subsequent development of BPD in preterm infants.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.590-600
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• 2003

The matrix metalloproteinases (MMPs) are a family of enzymes responsible for degrading connective tissue. MMPs catalyze the breakdown of collagen from the extracellular matrix, leading to wrinkle formation and accelerated skin aging. Furthermore, ultraviolet irradiation causes increased expression of certain MMPs. In the extracellular matrix turnover, MMPs are interacting with endogenous regulators named tissue inhibitors of metalloproteinases (TIMPs). Using peptide substrate assays, it has been demonstrated that TIMP-MMP complexes interact highly specifically with $K_{i}$ values of 10$^{-9}$ -10$^{-16}$ M. Therefore applications for TIMP as inhibitor of collagen degradation are suggested for cosmetic anti-aging products to prevent wrinkle formation and loss of elasticity. To date four TIMP proteins (TIMP-1, TIMP-2, TIMP-3 and TIMP-4) have been identified which show a high degree in sequence similarity. The production of human TIMP-2, a 194-residue nonglycosylated protein, was performed by fed-batch culture of Escherichia coli. TIMP-2 accumulated in the bacterial cells in an insoluble form as inclusion bodies. The inclusion bodies were solubilized and the protein refolded to yield the native TIMP-2 in the active form. The integrity of the protein was confirmed by mass analysis, Edman sequencing and gel shift experiments with authentic samples. The inhibitory activity of the refolded and purified TIMP-2 was demonstrated with MMP-1 and MMP-2 assays using synthetic fluorogenic peptide substrates.s.