1.Role of carcinoembryonic antigen and cyclooxygenase-2 in the study of molecule incisal edge for colorectal cancer.
Xiao-dong YANG ; Chun-gen XING ; Zhi-dong ZHAO ; Wei GONG ; Yong-you WU ; Feng-yun ZHONG ; Xiao-dong LV ; Kui ZHAO
Chinese Journal of Gastrointestinal Surgery 2011;14(10):807-809
OBJECTIVETo investigate the expression of cyclooxygenase-2(COX-2) and CEA in the tissues adjacent to the tumor within different distances.
METHODSA total of 42 colorectal cancer tissues were collected.The adjacent tissues within 3 cm to the tumor were procured every 1 cm. Normal tissue was also collected. RNA was extracted and the expression of CEA and COX-2 was detected by RT-PCR.
RESULTSThe CEA mRNA levels of the tumor, the tissues of every 1 cm adjacent to the tumor, and the normal tissue were 135.2 ± 23.3, 78.2 ± 17.3, 75.9 ± 16.5, 56.2 ± 10.7, 52.3 ± 12.8, 18.2 ± 7.9, 16.2 ± 6.5, and 16.6 ± 7.0. The levels of COX-2 mRNA in above positions were 134.9 ± 31.1, 79.2 ± 20.2, 77.0 ± 20.5, 62.7 ± 21.9, 58.0 ± 18.1, 21.2 ± 10.3, 18.3 ± 7.6, and 17.1 ± 6.3. These data showed a decreasing trend of CEA and COX-2 as the distance increased from the tumor. The CEA mRNA levels showed positive correlation with the levels of COX-2 mRNA(r=0.725, P<0.01).
CONCLUSIONCEA and COX-2 may be considered to be used as biomarkers for the study of molecular resection margin of colorectal cancer.
Adult ; Aged ; Carcinoembryonic Antigen ; metabolism ; Colorectal Neoplasms ; genetics ; immunology ; pathology ; Cyclooxygenase 2 ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging
2.Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway.
Sunhee SHIN ; Seong Soo JOO ; Dongsun PARK ; Jeong Hee JEON ; Tae Kyun KIM ; Jeong Seon KIM ; Sung Kyeong PARK ; Bang Yeon HWANG ; Yun Bae KIM
Journal of Veterinary Science 2010;11(1):43-50
The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 microgram/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E2 (PGE2). EAG (1~10 microgram/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE2 production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50~500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE2 without affecting tumor-necrosis factor (TNF)-alpha and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE2, but did not alter TNF-alpha or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX-PGE2 pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases.
Angelica/*immunology
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Animals
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Cell Line
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Cyclooxygenase 1/genetics/*immunology
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Cyclooxygenase 2/genetics/*immunology
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Dinoprostone/genetics/immunology
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Inflammation/drug therapy/enzymology/*immunology
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Interleukin-6/blood
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Macrophages
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Male
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Mice
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Mice, Inbred ICR
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Nitric Oxide/blood
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Phytotherapy/*methods
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Plant Extracts/*pharmacology/therapeutic use
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Plant Roots/immunology
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RNA, Messenger/chemistry/genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Necrosis Factor-alpha/blood
3.Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury.
Yi MOU ; Yan-Lin JIAN ; Tong CHEN ; Zhang-Jian HUANG ; Yi-Xue QIAO ; Si-Xun PENG ; Da-Yong ZHANG ; Hui JI ; Yi-Hua ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2017;15(5):347-354
The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.
Acute Lung Injury
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drug therapy
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genetics
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immunology
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Animals
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Anti-Inflammatory Agents
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administration & dosage
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chemical synthesis
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Bronchoalveolar Lavage Fluid
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immunology
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Cyclooxygenase 2
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genetics
;
immunology
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Female
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Humans
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Interleukin-1beta
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genetics
;
immunology
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Interleukin-6
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genetics
;
immunology
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Lipopolysaccharides
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adverse effects
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Lung
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drug effects
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immunology
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Macrophages
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drug effects
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immunology
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Male
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Mice
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Mice, Inbred BALB C
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Neutrophils
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drug effects
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immunology
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Oleanolic Acid
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administration & dosage
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analogs & derivatives
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chemical synthesis
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Peroxidase
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genetics
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immunology
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RAW 264.7 Cells
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Tumor Necrosis Factor-alpha
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genetics
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immunology
4.Rottlerin enhances IL-1beta-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells.
Experimental & Molecular Medicine 2011;43(12):669-675
Cyclooxygenase-2 (COX-2) is an important enzyme in inflammation. In this study, we investigated the underlying molecular mechanism of the synergistic effect of rottlerin on interleukin1beta (IL-1beta)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1beta-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1beta significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL-1beta treatment drove sustained activation of p38 Mitogen-activated protein kinase (MAPK), which is involved in induced COX-2 expression. Also, a pharmacological inhibitor of p38 MAPK (SB 203580) and transient transfection with inactive p38 MAPK inhibited rottlerin and IL-1beta-induced COX-2 upregulation. However, suppression of protein kinase C delta (PKC delta) expression by siRNA or overexpression of dominant-negative PKC delta (DN-PKC-delta) did not abrogate the rottlerin plus IL-1beta-induced COX-2 expression. Furthermore, rottlerin also enhanced tumor necrosis factor-alpha (TNF-alpha), phorbol myristate acetate (PMA), and lipopolysaccharide (LPS)-induced COX-2 expression. Taken together, our results suggest that rottlerin causes IL-1beta-induced COX-2 upregulation through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells.
Acetophenones/*pharmacology
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Benzopyrans/*pharmacology
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Breast Neoplasms/drug therapy/*genetics/immunology
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Cell Line, Tumor
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Cyclooxygenase 2/*genetics
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Enzyme Activation/drug effects
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Enzyme Inhibitors/*pharmacology
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Female
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Gene Expression Regulation, Neoplastic/*drug effects
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Humans
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Interleukin-1beta/*immunology
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MAP Kinase Signaling System/drug effects
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Mallotus Plant/chemistry
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NF-kappa B/immunology
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Protein Kinase C-delta/antagonists & inhibitors
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Reactive Oxygen Species/immunology
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p38 Mitogen-Activated Protein Kinases/*immunology
5.Effects of mangiferin on cytokines in rats with chronic bronchitis and expression of macrophage COX-2 in mice.
Qin WANG ; Jiagang DENG ; Ke YANG ; Lancheng XU
China Journal of Chinese Materia Medica 2011;36(10):1348-1352
OBJECTIVETo explore the mechanism of anti-inflammatory effect of mangiferin.
METHODThe model of chronic bronchitis in rat was established by LPS + smoke. The activity of SOD, content of MDA and NO in BALF and serum, content of TNF-alpha and IL-8 were determined. The expression of RAW264.7 macrophage COX-2 mRNA induced by LPS in mice was detected by RT-PCR.
RESULTThe activity of SOD, the content of NO in BALF and serum in rat with chronic bronchitis were significantly higher with high, medium and low-dose of lg mangiferin (400,200,100 mg x kg(-1)), while the content of MDA, and the content of TNF-alpha and IL-8 in lung tissues were lower. The expression of RAW264.7 macrophage COX-2 mRNA induced by LPS was significantly reduced by mangiferin with 200,100, 50 micromol x L(-1).
CONCLUSIONThe anti-inflammatory mechanism of mangiferin is to relieve inflammation by raising the activity of SOD and content of NO and reducing the content of MDA and the expression of TNF-alpha, IL-8 and COX-2 mRNA.
Animals ; Bronchitis, Chronic ; drug therapy ; genetics ; immunology ; Cell Line ; Cyclooxygenase 2 ; genetics ; immunology ; Cytokines ; genetics ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Gene Expression ; drug effects ; Humans ; Macrophages ; drug effects ; enzymology ; immunology ; Male ; Mice ; Rats ; Rats, Sprague-Dawley ; Xanthones ; administration & dosage ; pharmacology
6.Chemo-preventive effect of Angelica sinensis' supercritical extracts on AOM/DSS-induced mouse colorectal carcinoma associated with inflammation.
Jing AN ; Xiao-Ning LI ; Bo-Chen ZHAO ; Qiong WANG ; Yi LAN ; Qing WU
China Journal of Chinese Materia Medica 2014;39(7):1265-1269
To study the chemo-preventive effect of the supercritical extracts from Angelica sinensis (SFE-AS) on induced colorectal carcinoma in mice by using the AOM/DSS-induced male mice colorectal carcinoma model, and discuss its possible action mechanism. Male Balb/c mice were subcutaneously injected with single dose of azoxymethane (AOM, 10 mg x kg(-1) body weight). One week later, they were given 2% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colorectal carcinoma. Each drug group was orally administered with supercritical extracts from Angelica sinensis at 15, 30, 60 mg x kg(-1) until the 17th week. The tumor incidence rate of the SFE-AS group, mice tumor-bearing quantity and tumor-bearing volume of the SFE-AS group were lower than that of the AOM/DSS model control group, which may be related with the significant reduction of PCNA, COX-2, iNOS in the AOM/DSS-induced mouse colorectal carcinoma model associated with inflammation by SFE-AS. According to the results of this study, SFE-AS showed an intervention effect in the incidence and development of AOM/DSS-induced mouse colorectal carcinoma associated with inflammation, and could be further used in chemo-preventive studies on human colorectal carcinoma.
Angelica sinensis
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chemistry
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Animals
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Azoxymethane
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adverse effects
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Colonic Neoplasms
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chemically induced
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genetics
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immunology
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prevention & control
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Colorectal Neoplasms
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chemically induced
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genetics
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immunology
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prevention & control
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Cyclooxygenase 2
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genetics
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metabolism
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Dextran Sulfate
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adverse effects
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Disease Models, Animal
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Drugs, Chinese Herbal
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administration & dosage
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Humans
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Male
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Mice
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Mice, Inbred BALB C
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Proliferating Cell Nuclear Antigen
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genetics
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immunology
7.A novel beta-glucan produced by Paenibacillus polymyxa JB115 induces nitric oxide production in RAW264.7 macrophages.
Zhi Qiang CHANG ; Joong Su LEE ; Mi Hyun HWANG ; Joo Heon HONG ; Hee Kyoung JUNG ; Sam Pin LEE ; Seung Chun PARK
Journal of Veterinary Science 2009;10(2):165-167
The effect of extracellular beta-(1-->3), (1-->6)-glucan, produced by Paenibacillus polymyxa JB115, on nitric oxide (NO) production in RAW264.7 macrophages was investigated. beta-glucan induced the production of NO by RAW264.7 macrophages in a concentration- and time-dependent manner. Moreover, beta-glucan stimulation increased the mRNA expression of iNOS, COX-2 and IL-6 in RAW264.7 macrophages in a concentration-dependent manner.
Animals
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Bacillus/*metabolism
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Cell Line
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Cyclooxygenase 2/biosynthesis/genetics
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Interleukin-6/biosynthesis/genetics
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Lipopolysaccharides/pharmacology
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Macrophages/*drug effects/enzymology/immunology
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Mice
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Nitric Oxide/*biosynthesis/immunology
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Nitric Oxide Synthase Type II/biosynthesis/genetics/metabolism
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RNA, Messenger/biosynthesis/genetics
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Reverse Transcriptase Polymerase Chain Reaction
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beta-Glucans/metabolism/*pharmacology
8.Differential regulation of inducible nitric oxide synthase and cyclooxygenase-2 expression by superoxide dismutase in lipopolysaccharide stimulated RAW 264.7 cells.
Ji Ae LEE ; Ha Yong SONG ; Sung Mi JU ; Su Jin LEE ; Hyung Joo KWON ; Won Sik EUM ; Sang Ho JANG ; Soo Young CHOI ; Jinseu PARK
Experimental & Molecular Medicine 2009;41(9):629-637
Inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) have been known to be involved in various pathophysiological processes such as inflammation. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the LPS-induced expression of iNOS, and COX-2 in RAW 264.7 cells. When a cell-permeable SOD, Tat-SOD, was added to the culture medium of RAW 264.7 cells, it rapidly entered the cells in a dose-dependent manner. Treatment of RAW 264.7 cells with Tat-SOD led to decrease in LPS-induced ROS generation. Pretreatment with Tat-SOD significantly inhibited LPS-induced expression of iNOS and NO production but had no effect on the expression of COX-2 and PGE2 production in RAW 264.7 cells. Tat-SOD inhibited LPS-induced NF-kappaB DNA binding activity, IkappaBalpha degradation and activation of MAP kinases. These data suggest that SOD differentially regulate expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells.
Animals
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Cell Line
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Cyclooxygenase 2/*genetics/metabolism
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Cytokines/immunology
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*Gene Expression Regulation
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Lipopolysaccharides/immunology/metabolism
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Mice
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Mitogen-Activated Protein Kinase Kinases/metabolism
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NF-kappa B/metabolism
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Nitric Oxide/metabolism
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Nitric Oxide Synthase Type II/*genetics/metabolism
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Reactive Oxygen Species/metabolism
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Superoxide Dismutase/*metabolism
9.Endoplasmic reticulum stress (ER-stress) by 2-deoxy-D-glucose (2DG) reduces cyclooxygenase-2 (COX-2) expression and N-glycosylation and induces a loss of COX-2 activity via a Src kinase-dependent pathway in rabbit articular chondrocytes.
Experimental & Molecular Medicine 2010;42(11):777-786
Endoplasmic reticulum (ER) stress regulates a wide range of cellular responses including apoptosis, proliferation, inflammation, and differentiation in mammalian cells. In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes. 2DG is well known as an inducer of ER stress, via inhibition of glycolysis and glycosylation. Treatment of 2DG in chondrocytes considerably induced ER stress in a dose- and time-dependent manner, which was demonstrated by a reduction of glucose regulated protein of 94 kDa (grp94), an ER stress-inducible protein, as determined by a Western blot analysis. In addition, induction of ER stress by 2DG led to the expression of COX-2 protein with an apparent molecular mass of 66-70kDa as compared with the normally expressed 72-74 kDa protein. The suppression of ER stress with salubrinal (Salub), a selective inhibitor of eif2-alpha dephosphorylation, successfully prevented grp94 induction and efficiently recovered 2DG-modified COX-2 molecular mass and COX-2 activity might be associated with COX-2 N-glycosylation. Also, treatment of 2DG increased phosphorylation of Src in chondrocytes. The inhibition of the Src signaling pathway with PP2 (Src tyrosine kinase inhibitor) suppressed grp94 expression and restored COX-2 expression, N-glycosylation, and PGE2 production, as determined by a Western blot analysis and PGE2 assay. Taken together, our results indicate that the ER stress induced by 2DG results in a decrease of the transcription level, the molecular mass, and the activity of COX-2 in rabbit articular chondrocytes via a Src kinase-dependent pathway.
Animals
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Cartilage, Articular/pathology
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Cells, Cultured
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Chondrocytes/drug effects/immunology/*metabolism/pathology
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Cyclooxygenase 2/genetics/*metabolism
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Deoxyglucose/*pharmacology
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Down-Regulation
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Endoplasmic Reticulum/drug effects/*metabolism/pathology
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Glycosylation/drug effects
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Inflammation
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Rabbits
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Signal Transduction/drug effects
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Stress, Physiological/drug effects/immunology
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src-Family Kinases/*metabolism
10.Triptolide inhibites Th17 cell differentiation via regulating cyclooxygenase-2/ prostaglandin E2 axis in synovial fibroblasts from rheumatoid arthritis.
An-Ping PENG ; Xiao-Yun WANG ; Jun-Hua ZHUANG
China Journal of Chinese Materia Medica 2014;39(3):536-539
Triptolide (TPT), an active compound extracted from Chinese herb Tripterygium wilfordii , has been used in therapy of rheumatoid arthritis (RA). In this study, after synovial fibroblasts from rheumatoid arthritis (RASFs) were treated with TPT, we investigated its effect on the differentiation of Th17 cells. Firstly, the mRNA level of cyclooxygenase (COX) wad detected by qRT-PCR and the protein level of prostaglandin E2 (PGE2) was tested by ELISA in RASFs treated with different concentrations (0, 10, 50, 100 nmol L-1 ) of TPT. Then after TPT pre-treated RASFs and RA CD4 + T cells wer e co-cultured for 3 days in the presence or absence of PGE2, IL-17 and IFN-gamma production in CD4 T cell subsets were detected by flow cytometry. The results showed TPT decreased the mRNA experssion of COX2 and the secretion of PGE2 in RASFs in a dose-dependent manner(P <0. 05). We further found that differentiation of Thl7 cells was downregulated in a dose-dependent manner, and exogenous PGE2 could reverse the inhibition of Th17 cell differentiation(P <0. 05). Taken together, our results demonstrated that TPT inhibited the mRNA level of COX2 and the secretion of PGE2 in RASFs, which partly led to impaired Th17 cell differentiation in vitro.
Arthritis, Rheumatoid
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drug therapy
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enzymology
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immunology
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Cell Differentiation
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drug effects
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Cell Line
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Cyclooxygenase 2
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genetics
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metabolism
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Dinoprostone
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metabolism
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Diterpenes
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pharmacology
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Epoxy Compounds
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pharmacology
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Fibroblasts
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drug effects
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immunology
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Gene Expression Regulation, Enzymologic
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drug effects
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Humans
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Middle Aged
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Phenanthrenes
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pharmacology
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Synovial Fluid
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drug effects
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Th17 Cells
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drug effects
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pathology