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1.
Lee J Banu SK Nithy TK Stanley JA Arosh JA 《Molecular and cellular endocrinology》2012,348(1):211-223
Prostaglandin E2 (PGE2) plays pleiotropic roles at fetal-maternal interface during establishment of pregnancy. The objectives of the study were to: (i) determine regulation of PGE2 receptors EP1, EP2, EP3, and EP4 in the endometrium during the estrous cycle and early pregnancy; and (ii) understand endometrial epithelial and stromal cell-specific hormonal regulation of EP2 and EP4 in sheep. Results indicate that: (i) early pregnancy induces expression of EP2 and EP4 but not EP1 and EP3 proteins in the endometrium on days 12-16 compared to that of estrous cycle; (ii) intrauterine infusion of interferon tau (IFNT) increases expression of EP2 and EP4 proteins in endometrium; and (iii) IFNT activates distinct epithelial and stromal cell-specific JAK, EGFR, ERK1/2, AKT, or JNK signaling module to regulate expression of EP2 and EP4 proteins in the ovine endometrium. Our results indicate a role for EP2 and EP4-mediated PGE2 signaling in endometrial functions and establishment of pregnancy in ruminants. 相似文献
2.
Badawi AF Badr MZ 《International journal of cancer. Journal international du cancer》2003,103(1):84-90
Cyclooxygenase-2 (COX-2) expression and peroxisome proliferator-activated receptor-gamma (PPARgamma) inactivation are linked to increased risk of human breast cancer. The purpose of our study was to examine the relationship between COX-2 (with the resulting prostaglandins E(2), PGE(2)) and PPARgamma (and its natural endogenous ligand 15-Deoxy-Delta(12,14)-prostaglandin J(2), 15d-PGJ(2)) at various stages during the development of human breast cancer and its progression to metastasis. Human breast tissue specimens were collected from normal breasts or from individuals with fibrocystic disease and served as controls (n = 22). Tissues were also collected from uninvolved (n = 25), tumor (n = 25) and lymph node metastasis (n = 15) regions from breast cancer patients. COX-2 and PPARgamma mRNA expression were increased and downregulated, respectively, in tissues from cancer patients compared to controls. Metastatic tissues tended to have higher alterations compared to non-metastatic tissues (p < 0.05). These altered expressions in COX-2 and PPARgamma were paralleled by increases in the tissue levels of PGE(2) and decreases in 15d-PGJ(2). A significant inverse correlation was found between PGE(2) and 15-d-PGJ(2) (r = -0.51, p < 0.05). Significant correlations (p < 0.05) were also obtained between COX-2 and PPARgamma mRNA (inverse, r = -0.72) and between COX-2 and PGE(2) (direct, r = 0.68). Increases in COX-2 mRNA expression and levels of PGE(2) and down-regulation of PPARgamma mRNA expression and 15d-PGJ(2) levels were characterized as predictors of breast cancer risk (p < 0.05). Our results suggest that the altered expression of COX-2 and PPARgamma and the subsequent modulation in the tissue levels of PGE(2) and 15-d-PGJ(2) may influence the development of human breast cancer and its progression to metastasis. 相似文献
3.
Basu S 《Medicinal research reviews》2007,27(4):435-468
Prostaglandin F2alpha (PGF2alpha), a foremost stable vasoactive cyclooxygenase (COX)-catalyzed prostaglandin, regulates a number of key physiological functions such as luteolysis, ovarian function, luteal maintenance of pregnancy, and parturition as a constitutive part of ongoing reproductive processes of the body. It has recently been implicated in the regulation of intricate pathophysiological processes, such as acute and chronic inflammation, cardiovascular and rheumatic diseases. Since the discovery of a second isoform of COXs, it has been shown that PGF2alpha can be formed in vivo from arachidonic acid through both isoforms of COXs, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Being synthesized in various parts of the body, it metabolizes instantly to a number of rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently excretes into the urine. 15-Keto-dihydro-PGF2alpha, a major stable metabolite of PGF2alpha that reflects in vivo PGF2alpha biosynthesis, is found in larger quantities than its parent compound in the circulation and urine in basal physiological conditions, with short-lived pulses during luteolysis, induced termination of pregnancy and parturition, and is increased in tissues and various body fluids during acute, sub-chronic, and severe chronic inflammation. Further, the close relationship of PGF2alpha with a number of risk factors for atherosclerosis indicates its major role in inflammation pathology. This review addresses multiple aspects of PGF2alpha in addition to its emerging role in physiology to inflammation. 相似文献
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5.
Mario Sánchez-Borges Eric Capriles-Behrens Fernan Caballero-Fonseca 《Pediatric allergy and immunology》2004,15(4):376-380
Although largely investigated in adults, the issue of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in childhood is unsettled due to lack of sufficient data. The purpose of this study is to examine the clinical syndromes of hypersensitivity to NSAIDs in children and adolescents. We performed a review of relevant papers on cutaneous and respiratory adverse reactions triggered by NSAIDs in pediatric patients, and a recount of our own experience in 43 well-characterized NSAID-sensitive children with cutaneous reactions who were submitted to controlled oral challenges with NSAIDs and the new inhibitors of the enzyme isoform cyclooxygenase-2 (COX-2). Although it has been suggested that allergic and pseudoallergic reactions to NSAIDs in children occur rarely, their prevalence remains largely unknown due to the scarcity of studies. About 23% of NSAID-sensitive patients seen in our institutions are young patients aged 8-18 yr who more frequently develop facial angioedema as their main clinical manifestation. Most patients are atopic and show reactions to more than one drug (cross-reactors). Drugs that inhibit COX-2 with higher specificity than classic NSAIDs are better tolerated in young NSAID-hypersensitive patients. 相似文献
6.
《Expert opinion on pharmacotherapy》2013,14(2):277-286
Nimesulide is a NSAID with good anti-inflammatory, analgesic and antipyretic activities expected of such compounds. However, in addition it has some unique therapeutic and pharmacological activities. The novel therapeutic aspects include a relatively low toxicity to the gastrointestinal tract and kidneys, it can be given to most patients who experience respiratory problems with other NSAIDs, and the onset of analgesia is comparatively quick. The main novel pharmacological actions obtained using nimesulide in vivo at therapeutic doses, or in vitro at concentrations within the therapeutic range of free (unbound) drug, include: a preferential inhibition of prostaglandin synthesis via COX-2, and reductions in cytokine action/release, histamine release, the release of enzymes that degrade cartilage, and the release of superoxide anions and other toxic substances from neutrophils. Interactions with other drugs are few and of little or no clinical significance. 相似文献
7.
Saba Aid Afonso C Silva Eduardo Candelario-Jalil Sang-Ho Choi Gary A Rosenberg Francesca Bosetti 《Journal of cerebral blood flow and metabolism》2010,30(2):370-380
Cyclooxygenases (COX) -1 and -2 are key regulators of innate immune responses. We recently demonstrated that the expression of proinflammatory cytokines and chemokines is reduced in COX-1 null (−/−), and increased in COX-2−/− mice compared with their respective wild type controls during lipopolysaccharide (LPS)-induced innate immune activation. As chemokines are involved in leukocyte recruitment into the inflamed brain, we hypothesized that COX-1 and COX-2 deletion will differentially modulate blood–brain barrier (BBB) permeability in response to LPS. In the present study, using quantitative magnetic resonance imaging, we found that LPS-induced BBB disruption was exacerbated in COX-2−/− versus COX-2+/+ mice. In the hippocampus and cortex of LPS-treated mice, matrix metalloproteinase (MMP)-3 activity was significantly decreased in COX-1−/− mice, whereas in COX-2−/− mice the activity of both MMP-9 and MMP-3, known to mediate BBB breakdown, was increased. Brain mRNA expression of the leukocyte attracting chemokine Cxcl10, the intercellular interaction molecule Icam-1, the pan-leukocyte marker Cd45 was increased in COX-2−/− versus COX-2+/+ mice, whereas Cxcl10 and Cd45 mRNA expression was decreased in COX-1−/− versus COX-1+/+ mice after LPS. Altogether, these results indicate that COX-2 activity modulates MMP-9 and-3 activities and is necessary to maintain BBB integrity during toll-like receptor 4-dependent innate immune activation. 相似文献
8.
目的 探讨环氧合酶-2(COX-2)在胆囊癌组织中的表达及其临床意义.方法 :应用免疫组织化学方法分别检测41例胆囊癌、10例正常胆囊组织中COX-2的表达.结果 :胆囊癌组织中COX-2阳性表达率为65.9%(27/41),显著高于正常胆囊组织(30%,3/10),P=0.039.C0X-2主要表达于肿瘤细胞,癌周基质中的成纤维细胞、血管内皮细胞、巨噬细胞也有表达,其阳性表达与肿瘤TNM分期、淋巴结转移相关(p<0.05).结论 :COX-2的高表达参与胆囊癌的发生与发展. 相似文献
9.
Winnall WR Muir JA Liew S Hirst JJ Meachem SJ Hedger MP 《International journal of andrology》2009,32(5):542-555
Celecoxib (Celebrex), an inhibitor of cyclooxygenase-2 (COX-2; prostaglandin-endoperoxide synthase 2; EC 1.14.99.1), is widely used in the treatment of chronic inflammation and pain. COX-2 is constitutively expressed in the testis, where it is responsible for prostaglandin production, so inhibition of this enzyme should have effects on testicular function. The effects of administering celecoxib (oral with feed, 0.15% w/w) for 5 weeks on normal testis function and the response to low dose (0.1 mg/kg body weight) or high dose (5.0 mg/kg) lipopolysaccharide (LPS) were examined in adult male rats. Celecoxib caused a 60% reduction in testicular interstitial fluid (IF) prostaglandin E(2) (PGE(2)) concentrations, accompanied by a compensatory increase in COX-2 mRNA expression. Celecoxib increased IF volume by 30%, but had no effect on testis weight, testis morphology or serum testosterone levels. In the celecoxib-fed rats, the dose-dependent inhibitory effects of LPS on testis weight, IF volume and serum testosterone levels were significantly diminished. However, celecoxib had no effect on COX-2 protein levels or LPS-induced expression of the inflammatory mediators interleukin-1beta, tumour necrosis factor-alpha or inducible nitric-oxide synthase. A similar lack of inhibition of LPS-induced cytokine expression by another COX-2 inhibitor, NS-398, was observed in vitro. These data indicate that celecoxib reduces intratesticular activity of COX-2 (as indicated by PGE(2) levels) and inhibits IF formation in the testis, but has no appreciable effect on steroidogenesis or spermatogenesis, at least in the short term. Celecoxib does not appear to alter the ability of the testis to mount an inflammatory response but opposes the deleterious effects of inflammation on IF formation and testosterone production. These results indicate significant roles for products of the COX-2 pathway in testicular vascular control and steroidogenesis, which may have implications for men with marginal fertility taking celecoxib for extended periods, but also highlight the potential of this drug to ameliorate testicular damage caused by systemic or local inflammation. 相似文献
10.
A number of drugs were assessed for their ability to inhibit stimulus-evoked prostanoid synthesis in cultured glia. These
drugs included non-selective cyclooxygenase (COX) inhibitors and those considered to be selective for the inducible isoform
of this enzyme (COX-2). Experiments were carried out on normal cultures and those which had been maintained in serum-free
growth medium for four days then re-exposed to serum for a further seven days. All of the drugs tested elicited concentration-dependent
inhibitions of arachidonic acid (AA)-stimulated thromboxane B2 (TXB2) accumulation in normal cultures with the following rank order of potency: indomethacin > piroxicam > nimesulide = NS398
> ibuprofen ≫ aspirin > paracetamol. In cultures which had been deprived of serum for four days, basal and AA-stimulated TXB2 production was considerably reduced, as was the amount of COX immunoreactivity determined by Western blotting. Basal and
AA-stimulated TXB2 production together with COX immunoreactivity were restored to control levels by the re-addition of serum to serum-deprived
cultures for 7 days. In these cultures, the rank order of potency was: indomethacin > piroxicam ≫ ibuprofen > nimesulide =
NS398 ≫ aspirin > paracetamol; however, there were marked charges in the apparent IC50 values for particular drugs. Indomethacin, piroxicam and aspirin were very similar to control, but the potencies of ibuprofen
(3-fold), NS398 (30-fold) and nimesulide (40-fold) were found to be decreased when compared to control. Paracetamol, on the
other hand, was found to be almost 3-fold more potent under these conditions. Glia appear to express a COX with a novel sensitivity
to particular inhibitors following serum deprivation and re-addition. 相似文献