Disease relevance of Ptges2

• We conclude that radiation injury results in increased Cox-1 levels in crypt stem cells and their progeny, and that PGE2 produced through Cox-1 promotes crypt stem cell survival and proliferation [1].
• Here we report that PGE2 treatment of human colon cancer cells leads to increased clonogenicity of HCA-7, but not HCT-116 cells [2].
• Although PGE2 enhances intestinal adenoma growth in Apcmin mice, the mechanism(s) by which it accelerates tumor growth is not completely understood [3].
• Prostaglandin E2 was increased in polyps compared with normal tissue, and both COX-1 and COX-2 contributed to the PGE2 produced [4].
• These data indicate that a major antitumor mechanism of action of celecoxib is inhibition of COX-2-derived prostaglandins, particularly PGE2, and suggest celecoxib as a novel therapeutic agent for human head and neck cancer [5].

Psychiatry related information on Ptges2

• Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2alpha, correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease [6].
• These results suggest that ATP release during neuronal excitation or injury can enhance the inflammatory effects of cytokines on PGE2 production and may contribute to chronic inflammation seen in Alzheimer's disease [7].
• These results suggested that PGE2 affects host defense mechanisms against E. coli infection through modulation of cytokine production and gammadelta T cell accumulation [8].
• Prenatal exposure to PGE2 and PGF2 alpha on days 11-17 of gestation (the critical period of the differentiation) increased the anogenital distance of the female fetuses in a dose-dependent manner [9].
• On the other hand, PGE2, PGA1, PGA2 and PGB2 also caused a decrease in locomotor activity [10].

High impact information on Ptges2

• Although prostaglandin E2 (PGE2) is produced substantially in skin exposed to antigen, its role remains unclear [11].
• PGE2-EP4 signaling thus facilitates initiation of skin immune responses by promoting the migration and maturation of Langerhans cells [11].
• To evaluate the physiologic role of the PGE2 EP2 receptor subtype, we created mice with targeted disruption of this gene (EP2-/-) [12].
• The protection of cells in the upper intestine against digestion by pancreatic trypsin depends on the prostanoid prostaglandin E2 (PGE2) and is mediated by protease-activated receptors in the epithelium [13].
• As the airway epithelium is morphologically similar and also expresses one of these receptors, PAR2, and is a major source of PGE2, we reasoned that bronchial epithelial PAR2 might also participate in prostanoid-dependent cytoprotection in the airways [13].

Chemical compound and disease context of Ptges2

• PGE2 synthesis correlates with the onset of proteinuria and increased Pgc following reduced nephron mass [14].
• The results suggest that alteration of the resveratrol molecule to generate DMU-212 does not abrogate its ability to decrease adenoma number in Apc(Min+) mice or to interfere with PGE-2 generation in cells [15].
• Macrophage prostaglandin E2 (PGE2) production is important in cellular immune suppression and in affecting the potential development of sepsis after trauma [16].
• We have reported that cadmium (Cd) stimulates bone resorption via prostaglandin E2 (PGE2), which is mainly produced in osteoblasts [17].
• Nitric oxide (NO) and prostaglandin E2 (PGE2) are two of the major intrarenal vasodilators, which protect kidney from ischemia [18].

Biological context of Ptges2

• Additionally, PGE2 inhibits programmed cell death caused by SC-58125 and induces Bcl-2 expression, but did not affect Bcl-x or Bax expression in human colon cancer (HCA-7) cells [2].
• We investigated whether transformation of mammary cells was associated with up-regulation of Cox-2 as a basis for increased production of prostaglandin E2 (PGE2) by these cells [19].
• Therefore, decreased cell death caused by PGE2 would enhance the tumorigenic potential of intestinal epithelial cells [2].
• Here we have used mPGES-1 wild type, heterozygote, and null mice to assess the impact of reduction or absence mPGES-1 protein on the production of PGE2 and other prostaglandins in lipopolysaccharide (LPS)-treated macrophages and mice [20].
• As cellular stress induces both genes and their respective end products in pancreatic beta-cells, we evaluated the role of 12-hydroxyeicosatetraenoic acid (HETE) on COX-2 gene expression, protein expression, and prostaglandin E2 (PGE2) production [21].

Anatomical context of Ptges2

• COX-1, though present, appears not to participate significantly in stimulus-induced PGE2 production in P388D1 macrophages [22].
• IFN-gamma-producing CD4 T cells in spleens obtained from TA3-Ha tumor-bearing mice were significantly reduced compared with TA3-St tumor-bearing mice, suggesting that mucins cause PGE2-mediated immune suppression [23].
• Expression of COX2 mRNA and protein and production of PGE2 were elevated in peritoneal macrophages stimulated with epiglycanin, which is a mucin-like glycoprotein produced by TA3-Ha cells [23].
• We conclude that inhibition of COX-2/PGE2 suppresses Treg cell activity and enhances antitumor responses [24].
• Total cyclic AMP (cAMP) levels were reduced in Ep2-/- mammary glands suggesting that PGE2 signaling via the EP2 receptor activates the Gs/cAMP/protein kinase A pathway [25].

Associations of Ptges2 with chemical compounds

• The indomethacin dose response for inhibition of PGE2 production and reduction of crypt survival were similar [1].
• Secretory phospholipase A2 (sPLA2) is the major effector involved in arachidonic acid (AA) mobilization and prostaglandin E2 (PGE2) production during stimulation of P388D1 macrophages with the inflammatory stimuli bacterial lipopolysaccharide and platelet-activating factor [22].
• NNK increased plasma prostaglandin E2 (PGE2) basal levels by 413%, whereas ASA attenuated this elevation in a dose-response manner (r2 = 0.99) [26].
• COX-2-derived prostaglandin E2 (PGE2) is the most abundant prostaglandin found in several gastrointestinal malignancies [3].
• Increasing PGE2 and LTB4 levels by 44% with dietary arachidonic acid supplementation had no effect on tumor number or size [27].

Physical interactions of Ptges2

• Thus, PGE2 contributes to disease progression at least in part by binding to the EP4 receptor [28].
• LA blocked IL-1-induced PGE2 production even in the presence of arachidonic acid, without affecting the expression of COX-2 and membrane-bound PGE2 synthase [29].
• These results suggest that PGE2 contributes to colon carcinogenesis through binding to the EP1 receptor [30].
• Prostaglandin E2 (PGE2) is a potent lipid molecule with complex proinflammatory and immunoregulatory properties [31].
• PGE2 or PGF2alpha interacts with specific G protein-coupled membrane receptors [32].

Enzymatic interactions of Ptges2

• The membrane fraction containing recombinant mPGES-1 catalyzed the isomerization of PGH2 to PGE2 in the presence of GSH with K(m) values of 130 microM for PGH2 and 37 microM for GSH, a turnover number of 600 min(-1), and a k(cat)/K(m) ratio of 4.6 min(-1) microM(-1) [33].
• A number of 1,5-diarylimidazoles has been synthesized and evaluated for their inhibitory activities of COX-2 catalyzed PGE2 production [34].

Regulatory relationships of Ptges2

• We herein demonstrate that PGE2 in stimulated P388D1 cells is accounted for by the inducible cyclooxygenase (COX)-2 [22].
• In vivo, mPGES-1 deletion abolished the LPS-stimulated production of PGE2 in spleen, kidney, and brain [20].
• COX-2 was induced and PGE2 content was increased in the affected dorsal root ganglia at the stage of acute herpetic pain [35].
• However, other temporal events are likely to regulate such processes and as prostaglandin E2 (PGE2) is ubiquitous during inflammation this study tested the hypothesis that PGE2 was capable of directly modulating cytokine-induced NK cell IFN-gamma synthesis in the absence of other immune cells [36].
• These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and PGE2 in macrophages by inhibiting iNOS and COX-2 expression [37].

Other interactions of Ptges2

• Administration of sulindac (320 ppm) to Min/+ mice reduced the tumor number by 95% but did not alter the levels of PGE2 and LTB4 in intestinal tissues [27].
• Thioglycollate-elicited peritoneal macrophages with mPGES-1 deficiency were found to lose their ability to produce PGE2 upon LPS stimulation [20].
• Peptidoglycan-induced IL-6 production in RAW 264.7 macrophages is mediated by cyclooxygenase-2, PGE2/PGE4 receptors, protein kinase A, I kappa B kinase, and NF-kappa B [38].
• Migration of poorly migratory MCF-7 cells remained unaffected with either PGE2 or EP4 antagonist [39].
• In conclusion, PGE2 derived from either COX-1 or -2 is involved in regulation of gastric mucosal inflammation and contributes to maintenance of mucosal integrity during H. pylori infection via inhibition of TNF-alpha expression [40].

Analytical, diagnostic and therapeutic context of Ptges2

• We report here that 1483 human head and neck xenograft tumors express COX-2 similar to the pattern observed in human solid tumors and that COX-2 activity produces high levels of prostaglandin E2 (PGE2) [5].
• Amounts of intratumoral PGE2 were quantified by enzyme immunoassay [41].
• Treatment with indomethacin, a potent inhibitor of PG biosynthesis, inhibited UV-induced ear swelling, abrogated local immunosuppression, and decreased the amount of PGE2 in the ear skin of XPA-deficient mice [42].
• In superfusion media of spinal cord samples obtained from endotoxin treated mice, the concentrations of immunoreactive PGE2 and PGD2 were higher than in the control group suggesting enhanced spinal PG biosynthesis after endotoxin treatment [43].
• CM of activated encephalitogenic cells induced production of PGE2 by RAW 264.7 cells, as determined by ELISA, and Western blots identified the presence of the 70-80-kDa inducible COX (COX-2) protein [44].

References