• Title, Summary, Keyword: COX-2

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Cyclooxygenase-2 Can Modulate ICAM-1 Expression in Aorta or Heart Tissues of Rats Treated with Synthetic Estrogen or Soy-isoflavones

  • Kim Young Min;Lee Sung-Ok;Park Ock Jin
    • Environmental Mutagens and Carcinogens
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    • v.25 no.4
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    • pp.143-149
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    • 2005
  • The identification of COX-2 (cyclooxygenase-2) has led to potential novel insights on disease pathogenesis (atherosclerosis, cancer, Alzheimer's disease) and the regulation of normal organ function. The present in vivo study with estrogen or soy-isoflavones has provided evidence for the association between COX-2 and ICAM-1 (Intercellular adhersion molecule-1). In the system of mature female rats, soy-isoflavones exerted more pronounced effect on ICAM-1 inhibitory and COX-2 stimulatory effect than estrogen. In the system of ovariectomized estrogen deficient rats, the down-regulatory properties of soy-isoflavones on ICAM-1 was less evident, whereas estrogen exerted the inhibitory activity. These results demonstrate that COX-2 limits adhersion molecule expression on rat aorta cells and suggest that COX-2 may play a protective role in cardiovascular system in mature female rats. Soy-isoflavones appear to have beneficial effect on vascular systems through modulation of ICAM-1 and COX-2, and these molecules appeared to be closely associated.

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Ectopic Expression of Caveolin-1 Induces COX-2 Expression in Rabbit Articular Chondrocytes via MAP Kinase Pathway

  • Kim, Song-Ja
    • IMMUNE NETWORK
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    • v.6 no.3
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    • pp.123-127
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    • 2006
  • Background: Caveolin-1 is a principal component of caveolae membranes in vivo. Although expression of caveolae structure and expression of caveolin family, caveolin-1, -2 and -3, was known in chondrocytes, the functional role of caveolae and caveolins in chondrocytes remains unknown. In this study, we investigated the role of caveolin-1 in articular chondrocytes. Methods: Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. Caveolin-1 cDNA was transfected to articular chondrocytes using LipofectaminePLUS. The cyclooxygenase-2 (COX-2) expression levels were determined by immunoblot analysis, immunostaining, immunohistochemistry, and prostaglandin $E_2\;(PGE_2)$ assay was used to measure the COX-2 activity. Results: Ectopic expression of caveolin-1 induced COX-2 expression and activity, as indicated by immunoblot analysis and $PGE_2$ assay. And also, overexpression of caveolin-1 stimulated activation of p38 kinase and ERK-1/-2. Inhibition of p38 kinase and ERK-1/-2 with SB203580 and PD98059, respectively, led to a dose-dependent decrease COX-2 expression and $PGE_2$ production in caveolin-1-transfected cells. Conclusion: Taken together, our data suggest that ectopic expression of caveolin-1 contributes to the expression and activity of COX-2 in articular chondrocytes through MAP kinase pathway.

Src Kinase Regulates Nitric Oxide-induced Dedifferentiation and Cyc1ooxygenase-2 Expression in Articular Chondrocytes via p38 Kinase-dependent Pathway

  • Yu, Seon-Mi;Lee, Won-Kil;Yoon, Eun-Kyung;Lee, Ji-Hye;Lee, Sun-Ryung;Kim, Song-Ja
    • IMMUNE NETWORK
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    • v.6 no.4
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    • pp.204-210
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    • 2006
  • Background: Nitric oxide (NO) in articular chondrocytes regulates dedifferentiation and inflammatory responses by modulating MAP kinases. In this study, we investigated whether the Src kinase in chondrocytes regulates NO-induced dedifferentiation and cyclooxygenase-2 (COX-2) expression. Methods: Primary chondrocytes were treated with various concentrations of SNP for 24 h. The COX-2 and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin $E_2\;(PGE_2)$ was determined by using a $PGE_2$ assay kit. Expression and distribution of p-Caveolin and COX-2 in rabbit articular chondrocytes and cartilage explants were determined by immunohistochemical staining and immunocytochemical staining, respectively. Results: SNP treatment stimulated Src kinase activation in a dose-dependent manner in articular chondrocytes. The Src kinase inhibitors PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine], a significantly blocked SNP-induced p38 kinase and caveolin-1 activation in a dose-dependent manner. Therefore, to determine whether Src kinase activation is associated with dedifferentiation and/or COX-2 expression and $PGE_2$ production. As expected, PP2 potentiated SNP-stimulated dedifferentiation, but completely blocked both COX-2 expression and $PGE_2$ production. And also, levels of p-Caveolin and COX-2 protein expression were increased in SNP-treated primary chondrocytes and osteoarthritic and rheumatoid arthritic cartilage, suggesting that p-Caveolin may playa role in the inflammatory responses of arthritic cartilage. Conclusion: Our previously studies indicated that NO caused dedifferentiation and COX-2 expression is regulated by p38 kinase through caveolin-1 (1). Therefore, our results collectively suggest that Src kinase regulates NO-induced dedifferentiation and COX-2 expression in chondrocytes via p38 kinase in association with caveolin-1.

Associations between Single Nucleotide Polymorphisms of COX-2 and MMP-2 Genes and Colorectal Cancer Susceptibility in the Saudi Population

  • Shalaby, Manal Ali;Nounou, Howaida Attia;Alanazi, Mohammad Saud;Alharby, Othman;Azzam, Nahla;Saeed, Hesham Mahmoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4989-4994
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    • 2014
  • Background: It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. Materials and Methods: This research evaluated risk of association of the SNPs, including genes for COX-2 (AIG transition at +202) and MMP-2 (Crr transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. Results and Conclusions: Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=O.0121. On the other hand in our study, there was no significant association between genotype distribution ofthe COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency ofthe mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions ofCOX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.

NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells (사람 치주인대세포에서 Lipopolysaccharide와 니코틴으로 유도된 iNOS와 COX-2 발현에 NFATc의 관여)

  • Lee, Sang-Im;Yu, Ji-Su
    • Journal of dental hygiene science
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    • v.15 no.6
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    • pp.753-760
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    • 2015
  • Although nuclear factor of activated T cell (NFAT) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of NFAT on the proinflammatory mediators activated by lipopolysaccharide (LPS) plus nicotine stimulation in human periodontal ligament cells (hPDLCs). The production of nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NFAT proteins was evaluated by Western blot analysis. LPS plus nicotine synergistically induced the production of NO and $PGE_2$ and increased the protein expression of iNOS, COX-2 and NFAT. Treatment with an NFAT inhibitor blocked the LPS plus nicotine-stimulated NO and $PGE_2$ release as well as the expression of iNOS and COX-2. Our data suggest that the LPS plus nicotine-induced inflammatory effects on hPDLCs may act through a novel mechanism involving the action of NFAT. Thus, NFAT may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.

Inhibitory Effects on the Enzymes Involved in the Inflammation by the Ethanol Extracts of Plant Foodstuffs (식물성 일반식품 자원의 에탄올 추출물이 염증 효소계에 미치는 영향)

  • Kwon, Eun-Sook;Kim, Il-Rang;Kwon, Hoon-Jeong
    • Korean Journal of Food Science and Technology
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    • v.39 no.3
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    • pp.348-352
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    • 2007
  • Inflammation is a complex process resulting from a variety of mechanisms. Combined inhibition of the activities of enzymes involved in the process may therefore be considered more important in anti-inflammatory property of plant extracts than any single contribution. In this study, the inhibitory effects of the ethanol extracts of thirty plant foods on the activities of secretory phospholipase $A_{2}$ ($sPLA_{2}$), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 12-lipoxygenase (12-LOX) were examined. Several legumes, mungbean sprout and some leaf vegetables inhibited the activity of $sPLA_2$, upstream enzyme of inflammation pathway. Only soybean sprout and mungbean sprout significantly inhibited 12-LOX activity. Although most of extracts inhibited the activities of both COX-1 and COX-2, water dropwort and amaranth showed selectivity for the inhibition of COX-2 over COX-1. Especially, mungbean showed anti-inflammatory property at both upstream and downstream of inflammation pathway with relatively low $IC_{50}$ values for $sPLA_{2}$ and COX-2 enzymes. Mungbean sprout exhibited inhibitory effects on all enzymes related to early and late inflammation and soybean sprout suppressed 12-LOX and COX-2 simultaneously, although the activities of these plants were showed at relatively high concentration. Therefore, mungbean, mungbean sprout, and soybean sprout appear to exhibit anti-inflammatory effects by combined inhibition of inflammatory enzymes.

Reduction of muscle cyclooxygenase-2 with transcutaneous electrical nerve stimulation and cold therapy in rats of carrageenan-induced inflammatory muscle pain (Carrageenan으로 유도된 염증성 근통증 흰쥐 모델에서 경피신경전기자극과 냉치료에 의한 비복근의 cyclooxygenase-2의 감소)

  • Paek, Yun-Woong;Chae, Yun-Won
    • Journal of Korean Physical Therapy Science
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    • v.9 no.1
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    • pp.89-94
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    • 2002
  • Prostaglandins are generated through two isoforms of the enzyme cyclooxygenase, constitutively expressed cyclooxygenase(COX)-1 and COX-2, which is induced at sites of inflammation. Inhibition of COX-2 is desirable as this may avoid side effects seen with NSAIDs. We examined the effects of transcutaneous electrical nerve stimulation and cold therapy on the levels of muscle cycloooxygenase-2 mRNA in rats of carrageenan-induced inflammatory. The method of behavioral assessment were paw withdrawal latency(PWL) and tail flick test(TFT). The COX-2 mRNA levels were quantified by reverse transcription-polymerase chain reaction (RT-PCR). Following the transcutaneous electrical nerve stimulation and cold therapy, PWL and TFT were increased and COX-2 mRNA expression in gastrocnemius muscles were decreased. These results suggest that a transcutaneous electrical nerve stimulation and cold therapy were good therapy for a muscle pain.

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Mechanism of P-glycoprotein Expression in the SGC7901 Human Gastric Adenocarcinoma Cell Line Induced by Cyclooxygenase-2

  • Gu, Kang-Sheng;Chen, Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2379-2383
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    • 2012
  • Objective: To investigate possible signal pathway involvement in multi-drug resistant P-glycoprotein (P-gp) expression induced by cyclooxygenase-2 (COX-2) in a human gastric adenocarcinoma cell line stimulated with pacliaxel (TAX). Methods: The effects of TAX on SGC7901 cell growth with different doses was assessed by MTT assay, along with the effects of the COX-2 selective inhibitor NS-398 and the nuclear factor-KB (NF-KB) pathway inhibitor pyrrolidine dithiocarbamate (PDTC). Influence on COX-2, NF-KB p65 and P-gp expression was determined by Western blotting. Results: TAX, NS-398 and PDTC all reduced SGC7901 growth, with dosedependence. With increasing dose of TAX, the expression of COX-2, p65 and P-gp showed rising trends, this being reversed by NS-398. PDTC also caused decrease in expression of p65 and P-gp over time. Conclusion: COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation.

Screening of Cyclooxygenase-2 (COX-2) Inhibitors from Natural Products (천연물로부터 사이클로옥시게나제-2 저해제 검색)

  • Moon, Tae-Chul;Chung, Kyu-Charn;Son, Kun-Ho;Kim, Hyun-Pyo;Kang, Sam-Sik;Chang, Hyeun-Wook
    • YAKHAK HOEJI
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    • v.42 no.2
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    • pp.214-219
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    • 1998
  • Tissue distributions and association of cyclooxygenase-2 (COX-2) with inflammatory have led us to search for COX-2 selective inhibitors from natural products. Conceptually, COX- 2 selective inhibitors should be expected to retain anti-inflammatory efficacy by inhibition of PGs production while reducing or eliminating the gastric, renal and hemostatic side effects commonly associated with NSAIDs use. Thus, a logical approach to the treatment of inflammatory diseases should involve the inhibitors of COX-2. To develop new COX-2 inhibitors from natural products, two hundred crude drugs were screened by inhibiting PGD2 generation in bone marrow derived mast cells (BMMC). Among them, 6 methanol extracts of crude drugs such as, Bletillae rhizoma, Aconiti kgreani rhizoma, Belamcandae rhizoma, Nelumbinis semen, Gleniae radix, Aurantii immatri pericarpium inhibited more than 85% of BMMC COX-2 activity at a concentration 2.5${\mu}$g/ml.

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Aspirin inhibits lipopolysaccharide-induced COX-2 expression and PGE2 production in porcine alveolar macrophages by modulating protein kinase C and protein tyrosine phosphatase activity

  • Duan, Yuzhong;Chen, Fanglin;Zhang, Anmei;Zhu, Bo;Sun, Jianguo;Xie, Qichao;Chen, Zhengtang
    • BMB Reports
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    • v.47 no.1
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    • pp.45-50
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    • 2014
  • Aspirin has been demonstrated to be effective in inhibiting COX-2 and $PGE_2$ in Alveolar macrophages (AMs). However, the mechanisms have not been fully understood. In the present study, we found that pretreatment with aspirin inhibited LPS-induced COX-2 and$PGE_2$ upregulation, $I{\kappa}B{\alpha}$ degradation, NF-${\kappa}B$ activation and the increase of PKC activity, but elevated LPS-induced the decrease of PTP activity. The PKC inhibitor calphostin C dramatically reduced the COX-2 mRNA and $PGE_2$ levels, but the PTP inhibitor peroxovanadium (POV) significantly increased the COX-2 mRNA and$PGE_2$ levels. Furthermore, the PTP inhibitor mitigated the inhibitory effect of aspirin on COX-2 and$PGE_2$ upregulation and NF-${\kappa}B$ activation, whereas the PKC inhibitor enhanced the inhibitory effects of aspirin on the production of COX-2 and$PGE_2$. Our data indicate a novel mechanism by which aspirin acts as a potent anti-inflammatory agent in alveolus macrophages and ALI.