BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are generally attributed to suppression cyclooxygenase enzymes, leading to decreased products of the arachidonic acid cascade. Since the discovery of two isoenzymes of cyclooxygenase, inhibition of cyclooxygenase-2 has been suggested to be responsible for therapeutic effects of NSAIDs without side effects. In the present study, to investigate the extent to peripheral nociception and inflammation of cyclooxygenase-1 and cyclooxygenase-2, diclofenac (non-selective inhibitor), SC-560 (selective cyclooxygenase-1 inhibitor) and NS-398 (selective cyclooxygenase-2 inhibitor) are injected intra-articularly on acute arthritic model in rats. METHODS: Arthritis was induced with 2% lamda-carrageenan (suspended in 50microliter normal saline) into the right knee joint cavity under enflurane anesthesia (2-4%). Before and after the injection, rats were allowed to walk freely through a pathway constructed to record weight load by means of 8 weight sensors (strain gauge type) attached to 8 plates which function independently. The weight load, diameter of both knee joints and weight of rat were measured at each test. At 4 hours and 30 minutes, diclofenac, SC-560 and NS-398 dissolved in 10% dimethyl sulfoxide were injected intra-articularly (50microgram/50microliter). RESULTS: The weight loads increased in diclofenac group at 6 and 9 hours and in NS-398 group at 24 and 48 hours after induction of arthritis. The diameter ratio decreased in diclofenac group at 12 hours after induction of arthritis. CONCLUSIONS: These results suggest that peripheral nociception and inflammation in acute model of arthritis in rats are likely related with both cyclooxygenase-1 and cyclooxygenase-2 pathways.
Anesthesia ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Arachidonic Acid ; Arthritis ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Diclofenac* ; Dimethyl Sulfoxide ; Enflurane ; Inflammation ; Isoenzymes ; Knee Joint ; Nociception ; Prostaglandin-Endoperoxide Synthases ; Rats*

OBJECTIVE: To determine whether cyclooxygenase (COX)-1 and COX-2 are expressed differentially during the whole gestational period in the pregnant human uterine cervix and if they are involved in the process of labor. METHODS: Nine patients were matched for obstetrical history and maternal age were divided into an abortion group who aborted between 13 and 16 weeks(n=3), a preterm group who delivered between 20 and 37 weeks(n=3), and a term group who delivered between 37 and 42 weeks of gestation(n=3). Immediately after vaginal delivery cervical biopsy samples were obtained and immunohistochemically stained for COX-1 and COX-2 and the degree of staining was evaluated by H-scoring system. RESULTS: Expression of COX-1 and COX-2 was found in epithelial and stromal cells of uterine cervical tissues of preterm and term group. The immunohistochemical expression of COX-1 and COX-2 was strongest in the term group compared to the preterm group in stromal cells(HSCORE : 2.0 vs. 4.0 ; 2.0 vs. 3.0), and in epithelial cells(HSCORE : 1.0 vs. 3.0 ; 1.0 vs. 3.0). CONCLUSION: Although small amount of the groups were investigated, in the pregnant human uterine cervix, COX-1 and COX-2 are found to be expressed, and both shows the strongest expression in term cervical tissue. It is suggested that the uterine cervix, under the control of prostaglandins, is actively involved in the process of labor, and it is thought that the role of COX-1 and COX-2 is more important in parturition process with advancing gestational age.
Biopsy ; Cervix Uteri* ; Cyclooxygenase 1* ; Cyclooxygenase 2 ; Female ; Gestational Age ; Humans* ; Maternal Age ; Parturition ; Pregnancy ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins ; Stromal Cells

BACKGROUND: All currently available nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 and cyclooxygenase-2 and exhibit many complications. It has been suggested that the anti-inflammatory and also most of the analgesic effects of NSAlDs result from an inhibition of arachidonic acid metabolites synthesised via cyclooxygenase-2. In the present study, the extent of analgesic and anti-inflammatory effects of ibuprofen (a non-selective cyclooxygenase inhibitor), indomethacin (a selective cyclooxygenase-1 inhibitor) and NS-398 (a selective cyclooxygenase-2 inhibitor) are investigated in on acute model of arthritis in rats by a behavior test and pathologic examination. METHODS: Arthritis was induced with 2% kaolin and 3% carrageenan into the right knee joint cavity under enflurane anesthesia (2 - 4%). Before and after the injection, rats were allowed to walk freely through a pathway, constructed to record weight load by means of 8 weight sensors attached to 8 plates which function independently. Weight bearing, the weight of rat and the diameter of the knee joint were measured serially before and after the injection. At 6 hours after the injection, ibuprofen, indomethacin and NS-398 were injected intraperitoneally (1, 5 and 25 mg/kg/ml). RESULTS: In the control group, weight bearing decreased maximally and the weight bearing ratio increased maximally at 6 hours after inflammation and the diameter ratio increased maximally 1 day after inflammation. There were improvements in weight bearing with ibuprofen, indomethacin and NS-398 in a dose-dependent manner at 8, 10 and 12 hours after induction of arthritis. NS-398 demonstrated better analgesic and anti-inflammatory effects than ibuprofen or indomethacin at a low dose (1 mg/kg). In contrast to NS-398, significant analgesic effects of indomethacin on the behavior test was not shown at a low dose. CONCLUSIONS: These results suggest that the selective cyclooxygenase-2 inhibitor plays an important role as an analgesic and anti-inflammatory drug.
Anesthesia ; Animals ; Arachidonic Acid ; Arthritis* ; Carrageenan ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Enflurane ; Ibuprofen* ; Indomethacin* ; Inflammation ; Kaolin ; Knee Joint ; Prostaglandin-Endoperoxide Synthases ; Rats* ; Weight-Bearing

Armeniacae semen has been used in traditional medicine for the treatment of pain and inflammatory diseases. Amygdalin is the major compound of Armeniacae semen, and it is used for treatment of pain and cancers. In the present study, we compared the effects of aqueous extract of Armeniacae semen and a solution of amygdalin extracted from Armeniacae semen on the lipopolysaccharide (LPS)-stimulated cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA expressions in mouse BV2 microglial cells. We also compared the effects of these compounds on the prostaglandin E2 synthesis and the nitric oxide production in mouse BV2 microglial cells. In the present results, Armeniacae semen and amygdalin suppressed prostaglandin E2 synthesis and nitric oxide production by inhibiting the LPS-induced enhancement of COX-2 mRNA and iNOS mRNA expressions in mouse BV2 cells. For the COX-1 expression, Armeniacae semen showed more potent suppression effect compared to the amygdalin. However, amygdalin more potently suppressed the LPS-induced COX-2 mRNA expression compared to aqueous extract of Armeniacae semen. In the case of iNOS mRNA expression, Armeniacae semen and amygdalin showed similar suppressing effects. For the LPS-induced PGE2 synthesis, amygdalin showed more potent suppressing effect, meanwhile, Armeniacae semen and amygdalin showed similar suppressing effect on NO production. Based on the present results, amygdalin may exert anti-inflammatory and analgesic effect though mainly the inhibition of COX-2 pathway, in contrast Armeniacae semen may exert such effect though both the inhibition of COX-2 and iNOS pathways.
Amygdalin ; Animals ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Dinoprostone ; Medicine, Traditional ; Mice ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Prostaglandin-Endoperoxide Synthases ; RNA, Messenger ; Semen

OBJECTIVE: The purpose of this study was to determine whether cyclooxygenase [COX]-1 and COX-2 are expressed in the pregnant human uterine cervix and if they are expressed differentially between preterm and term pregnancies. METHODS: Fourteen patients delivered between 29 and 41 weeks of gestation were matched for obstetrical history and maternal age were divided into a preterm group who delivered between 29 and 36 weeks [n=7], and a term group who delivered between 37 and 41 weeks of gestation [n=7]. Immediately after vaginal delivery cervical biopsy samples were obtained and immunohistochemicaly stained for COX-1 and COX-2 and the degree of staining was evaluated by H-scoring system. RESULTS: Expression of COX-1 and COX-2 was found in all epithelial and stromal cells of uterine cervical tissues of pregnancy. The expression of COX-1 and COX-2 was significantly stronger in the term group compared to the preterm group in epithelial cells [HSCORE : 2.14+/-0.69 vs. 1.14+/-0.38 ; 3.71+/-0.76 vs. 1.86+/-0.90, p<0.05], but there was no significant differences in stromal cells [HSCORE : 3.43+/-0.53 vs. 2.86+/-0.38 ; 2.43+/-0.53 vs. 2.57+/-0.98, p>0.05]. CONCLUSION: In the pregnant human uterine cervix, COX-1 and COX-2 are found to be expressed, and both are strongly expressed in the cervical epithelial cells of term pregnancies compared to preterm pregnancies. It is suggested that the uterine cervix, under the control of prostaglandins, is actively involved in the process of labor, and that the role of COX-2 in epithelium is particularly significant in term pregnancies compared to preterm pregnancies.
Biopsy ; Cervix Uteri* ; Cyclooxygenase 1* ; Cyclooxygenase 2 ; Epithelial Cells ; Epithelium ; Female ; Humans* ; Maternal Age ; Pregnancy* ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins ; Stromal Cells

BACKGROUND AND OBJECTIVES: A large body of evidence from a variety of experimental systems suggests that cyclooxygenase-2 (COX-2) is important in carcinogenesis. This study was to determine whether cyclooxygenase-1 (COX-1) and COX-2 were overexpressed in laryngeal squamous cell carcinoma, and discuss the possible causal role of COX-2 in the laryngeal squamous cell carcinoma formation. MATERIALS AND METHODS: Tissue samples from 21 pateints with laryngeal squamous cell carcinoma were analyzed by immunohistochemical staining. RESULTS: There was an elevation of COX-2 expression in laryngeal squamous cell carcinoma. Normal buccal mucosa biopsies and normal laryngeal epitheliums adjacent to laryngeal cancer showed nondetectable or weak staining for COX-2 protein. There is no difference in the expression of COX -1 in the normal buccal mucosa, normal laryngeal mucosa and laryngeal squamous cell carcinoma. CONCLUSION: There is an overexpression of COX-2, but not COX-1 in laryngeal squamous cell cancer. This may represent a causal role of COX-2 in the formation and proliferation of laryngeal squamous cell carcinoma. There may also be another role of selective COX-2 inhibition for treatment of laryngeal squamous cell carcinoma.
Biopsy ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cyclooxygenase 1* ; Cyclooxygenase 2 ; Laryngeal Mucosa ; Laryngeal Neoplasms ; Mouth Mucosa ; Neoplasms, Squamous Cell ; Prostaglandin-Endoperoxide Synthases*

BACKGROUND AND OBJECTIVES: Cyclooxygenase-2 (COX-2) is a key molecule in the biosynthesis of prostaglandins, which are important inflammatory mediators in human airway inflammatory diseases. This study was designed to investigate the effects of several COX inhibitors on the interleukin-1beta (IL-1beta)-mediated COX-2 expression in human airway epithelial cells. MATERIALS AND METHOD: We observed the effects of anti-inflammatory drugs such as budesonide, triamcinolone, dexamethasone, NS-398, indomethacin, salicylate and resveratrol on the IL-1beta-induced COX-2 expression in cultured human airway NCI-H292 epithelial cells. The levels of COX-2 mRNA and COX-2 protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: NS398, reveratrol and three corticosteroids strongly suppressed the IL-1beta-mediated COX-2 expression. However, indomethacin and salicylate did not inhibit or inhibited only weakly. CONCLUSION: The extent of IL-1beta-induced supression of COX-2 expression in the cultured human airway NCI-H292 epithelial cells depended on the kinds of anti-inflammatory drugs.
Adrenal Cortex Hormones ; Blotting, Western ; Budesonide ; Cyclooxygenase 2* ; Dexamethasone ; Epithelial Cells* ; Humans* ; Indomethacin ; Interleukin-1* ; Interleukin-1beta ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins ; RNA, Messenger ; Triamcinolone

No abstract available.
Prostaglandin-Endoperoxide Synthases

PURPOSE: The effects of PGE2 receptors (EP1, 2, 3, 4) on the proliferation of prostate cancer cells are still unclear. The degradation of the basement membrane by MMP-2, 7, 9 and TIMP-1, 2 is a critical point in tumor invasion and metastasis. We investigated the effects of PGE2 receptors concerning MMP and TIMP after the treatment of COX-2 inhibitors on prostate cancer cell-lines. MATERIALS AND METHODS: Two prostate cancer cell-lines, PC-3 and DU-145 cells were used in this study. RT-PCR were performed to detect the mRNA expression of EP1, 2, 3, 4, MMP-2, 7, 9 and TIMP-1, 2, MMP-7 was measured by ELISA after being treated with the selective EP2 agonist and EP4 agonist 10(-10), 10(-8), 10(-6) microM respectively. RESULTS: EP2, 3 and 4 mRNA were expressed in both cell-lines. After the NS-398 treatment, EP2 and EP4 mRNA expressions decreased in PC-3 cells. While only the MMP-7 mRNA expression decreased in PC-3 cells after NS-398 treatment, after NS-398 with selective EP2 agonist and EP4 agonist, MMP-7 mRNA expression increased. In PC-3 cells, selective EP2 agonist and EP4 agonist induced a significant dose-dependent increase in MMP-7 production in comparison to the NS-398 treatment group (control) in the conditioned ELISA medium. CONCLUSIONS: These results strongly suggest that COX-2, to some extent, contribute to prostate carcinogenesis at the EP2 and EP4 receptor, which could also be explained by increments of MMP-7 in PC-3 cells. Therefore, these findings show that selective EP inhibitor is useful in preventing specific disease progression in prostate cancer.
Basement Membrane ; Carcinogenesis ; Cyclooxygenase 2 Inhibitors ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Matrix Metalloproteinase 7 ; Neoplasm Metastasis ; Prostaglandin-Endoperoxide Synthases ; Prostate ; Prostatic Neoplasms ; Receptors, Prostaglandin E ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-1

BACKGROUND AND OBJECTIVES: Mucus hypersecretion is a major problem in inflammatory airway disease. Interleukin-1beta (IL-1beta) has been implicated in the pathogenesis of inflammatory airway diseases. This study was designed to investigate the signal transduction mechanism and the relationship between cyclooxygenase-2 (COX-2) expression and the IL-1beta-mediated MUC5AC secretion. MATERIALS AND METHOD: In cultured human airway NCI-H292 epithelial cells, the IL-1beta-mediated MUC5AC gene expression and mucin secretion were analyzed by reverse transcription-polymerase chain reaction and immunoassay. To identify the signal transduction pathway of the IL-1beta-mediated MUC5AC expression, we used specific inhibitors. RESULTS: IL-1beta induced COX-2 and MUC5AC expression at the mRNA and protein levels. Mucin secretion was blocked by NS398 and resveratrol, selective COX-2 inhibitors. Prostaglandin E2 (PGE2) directly induced MUC5AC expression at both mRNA and protein levels in a dose-dependent manner. Cells activated by IL-1beta showed increased extracellular-regulated protein kinase (ERK) 1/2 and p38 phosphorylation. IL-1beta-induced MUC5AC gene expression and mucin secretion were blocked by PD98059, the MEK/ ERK inhibitor and SB203580, the p38 inhibitor. Furthermore, inhibition of both mitogen-activated protein kinases (MAPKs) reduced the IL-1beta-induced COX-2 expression and PGE2 synthesis. Ro31-8220, the PKC inhibitors prevented the IL-1beta-induced COX-2 expression and mucin secretion. Also Ro31-8220 inhibited the IL-1beta-mediated MAPKs phosphorylation. CONCLUSION: IL-1beta-induced MUC5AC gene expression and mucin secretion are regulated through the sequential activation of PKC-ERK/ p38-COX-2-PGE2 in the human airway NCI-H292 epithelial cells.
Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Dinoprostone ; Epithelial Cells* ; Gene Expression* ; Humans* ; Immunoassay ; Interleukin-1 ; Interleukin-1beta ; Mitogen-Activated Protein Kinases ; Mucins* ; Mucus ; Phosphorylation ; Prostaglandin-Endoperoxide Synthases ; Protein Kinase C ; Protein Kinases ; RNA, Messenger ; Signal Transduction