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Gene Review

Ptges2  -  prostaglandin E synthase 2

Mus musculus

Synonyms: 0610038H10Rik, C79137, GATE-binding factor 1, GBF-1, GBF1, ...
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Disease relevance of Ptges2


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


Biological context of Ptges2


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


Physical interactions of Ptges2


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].


  1. Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1. Cohn, S.M., Schloemann, S., Tessner, T., Seibert, K., Stenson, W.F. J. Clin. Invest. (1997) [Pubmed]
  2. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Sheng, H., Shao, J., Morrow, J.D., Beauchamp, R.D., DuBois, R.N. Cancer Res. (1998) [Pubmed]
  3. Prostaglandin E2 enhances intestinal adenoma growth via activation of the Ras-mitogen-activated protein kinase cascade. Wang, D., Buchanan, F.G., Wang, H., Dey, S.K., DuBois, R.N. Cancer Res. (2005) [Pubmed]
  4. Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Chulada, P.C., Thompson, M.B., Mahler, J.F., Doyle, C.M., Gaul, B.W., Lee, C., Tiano, H.F., Morham, S.G., Smithies, O., Langenbach, R. Cancer Res. (2000) [Pubmed]
  5. Direct evidence for a role of cyclooxygenase 2-derived prostaglandin E2 in human head and neck xenograft tumors. Zweifel, B.S., Davis, T.W., Ornberg, R.L., Masferrer, J.L. Cancer Res. (2002) [Pubmed]
  6. Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies. Minghetti, L., Greco, A., Cardone, F., Puopolo, M., Ladogana, A., Almonti, S., Cunningham, C., Perry, V.H., Pocchiari, M., Levi, G. J. Neuropathol. Exp. Neurol. (2000) [Pubmed]
  7. Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents. Xu, J., Chalimoniuk, M., Shu, Y., Simonyi, A., Sun, A.Y., Gonzalez, F.A., Weisman, G.A., Wood, W.G., Sun, G.Y. Prostaglandins Leukot. Essent. Fatty Acids (2003) [Pubmed]
  8. Prostaglandin E2 protects against liver injury after Escherichia coli infection but hampers the resolution of the infection in mice. Takano, M., Nishimura, H., Kimura, Y., Washizu, J., Mokuno, Y., Nimura, Y., Yoshikai, Y. J. Immunol. (1998) [Pubmed]
  9. Prostaglandins masculinize the mouse genital tract. Gupta, C. Endocrinology (1989) [Pubmed]
  10. Protective effect of prostaglandins D2, E1 and I2 against cerebral hypoxia/anoxia in mice. Masuda, Y., Ochi, Y., Ochi, Y., Karasawa, T., Hatano, N., Kadokawa, T., Shimizu, M. Naunyn Schmiedebergs Arch. Pharmacol. (1986) [Pubmed]
  11. Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells. Kabashima, K., Sakata, D., Nagamachi, M., Miyachi, Y., Inaba, K., Narumiya, S. Nat. Med. (2003) [Pubmed]
  12. Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. Kennedy, C.R., Zhang, Y., Brandon, S., Guan, Y., Coffee, K., Funk, C.D., Magnuson, M.A., Oates, J.A., Breyer, M.D., Breyer, R.M. Nat. Med. (1999) [Pubmed]
  13. A protective role for protease-activated receptors in the airways. Cocks, T.M., Fong, B., Chow, J.M., Anderson, G.P., Frauman, A.G., Goldie, R.G., Henry, P.J., Carr, M.J., Hamilton, J.R., Moffatt, J.D. Nature (1999) [Pubmed]
  14. p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton. Martineau, L.C., McVeigh, L.I., Jasmin, B.J., Kennedy, C.R. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  15. Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4'-tetramethoxystilbene (DMU-212) on adenoma development in the Apc(Min+) mouse and cyclooxygenase-2 in human-derived colon cancer cells. Sale, S., Tunstall, R.G., Ruparelia, K.C., Potter, G.A., Steward, W.P., Gescher, A.J. Int. J. Cancer (2005) [Pubmed]
  16. Enhanced expression of cyclooxygenase-2 and prostaglandin E2 in response to endotoxin after trauma is dependent on MAPK and NF-kappaB mechanisms. Yan, Z., Stapleton, P.P., Freeman, T.A., Fuortes, M., Daly, J.M. Cell. Immunol. (2004) [Pubmed]
  17. Stimulative effect of cadmium on prostaglandin E2 production in primary mouse osteoblastic cells. Miyahara, T., Tonoyama, H., Watanabe, M., Okajima, A., Miyajima, S., Sakuma, T., Nemoto, N., Takayama, K. Calcif. Tissue Int. (2001) [Pubmed]
  18. Cyclosporine decreases prostaglandin E2 production in mouse medullary thick ascending limb cultured cells. Chang, C.T., Hung, C.C., Yang, C.W., Vandewalle, A., Wu, M.S. Transpl. Int. (2005) [Pubmed]
  19. Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells. Subbaramaiah, K., Telang, N., Ramonetti, J.T., Araki, R., DeVito, B., Weksler, B.B., Dannenberg, A.J. Cancer Res. (1996) [Pubmed]
  20. Deletion of microsomal prostaglandin E2 (PGE2) synthase-1 reduces inducible and basal PGE2 production and alters the gastric prostanoid profile. Boulet, L., Ouellet, M., Bateman, K.P., Ethier, D., Percival, M.D., Riendeau, D., Mancini, J.A., Méthot, N. J. Biol. Chem. (2004) [Pubmed]
  21. Induction of cyclooxygenase-2 gene in pancreatic beta-cells by 12-lipoxygenase pathway product 12-hydroxyeicosatetraenoic acid. Han, X., Chen, S., Sun, Y., Nadler, J.L., Bleich, D. Mol. Endocrinol. (2002) [Pubmed]
  22. Functional coupling between secretory phospholipase A2 and cyclooxygenase-2 and its regulation by cytosolic group IV phospholipase A2. Balsinde, J., Balboa, M.A., Dennis, E.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  23. Different progression of tumor xenografts between mucin-producing and mucin-non-producing mammary adenocarcinoma-bearing mice. Sugihara, I., Yoshida, M., Shigenobu, T., Takagi, H., Maruyama, K., Takeuchi, N., Toda, M., Inoue, M., Nakada, H. Cancer Res. (2006) [Pubmed]
  24. Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Sharma, S., Yang, S.C., Zhu, L., Reckamp, K., Gardner, B., Baratelli, F., Huang, M., Batra, R.K., Dubinett, S.M. Cancer Res. (2005) [Pubmed]
  25. The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia. Chang, S.H., Ai, Y., Breyer, R.M., Lane, T.F., Hla, T. Cancer Res. (2005) [Pubmed]
  26. Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Rioux, N., Castonguay, A. Cancer Res. (1998) [Pubmed]
  27. Sulindac causes rapid regression of preexisting tumors in Min/+ mice independent of prostaglandin biosynthesis. Chiu, C.H., McEntee, M.F., Whelan, J. Cancer Res. (1997) [Pubmed]
  28. The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. McCoy, J.M., Wicks, J.R., Audoly, L.P. J. Clin. Invest. (2002) [Pubmed]
  29. alpha-Lipoic acid inhibits inflammatory bone resorption by suppressing prostaglandin E2 synthesis. Ha, H., Lee, J.H., Kim, H.N., Kim, H.M., Kwak, H.B., Lee, S., Kim, H.H., Lee, Z.H. J. Immunol. (2006) [Pubmed]
  30. COX-2 and iNOS, good targets for chemoprevention of colon cancer. Watanabe, K., Kawamori, T., Nakatsugi, S., Wakabayashi, K. Biofactors (2000) [Pubmed]
  31. Prostaglandin E2 receptors of the EP2 and EP4 subtypes regulate activation and differentiation of mouse B lymphocytes to IgE-secreting cells. Fedyk, E.R., Phipps, R.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  32. Potential sites of prostaglandin actions in the periimplantation mouse uterus: differential expression and regulation of prostaglandin receptor genes. Yang, Z.M., Das, S.K., Wang, J., Sugimoto, Y., Ichikawa, A., Dey, S.K. Biol. Reprod. (1997) [Pubmed]
  33. Biochemical characterization of mouse microsomal prostaglandin E synthase-1 and its colocalization with cyclooxygenase-2 in peritoneal macrophages. Lazarus, M., Kubata, B.K., Eguchi, N., Fujitani, Y., Urade, Y., Hayaishi, O. Arch. Biochem. Biophys. (2002) [Pubmed]
  34. Synthesis and antiinflammatory activity of 1,5-diarylimidazoles. Tuyen, T.N., Sin, K.S., Kim, H.P., Park, H. Arch. Pharm. Res. (2005) [Pubmed]
  35. Involvement of cyclooxygenase-2 and EP3 prostaglandin receptor in acute herpetic but not postherpetic pain in mice. Takasaki, I., Nojima, H., Shiraki, K., Sugimoto, Y., Ichikawa, A., Ushikubi, F., Narumiya, S., Kuraishi, Y. Neuropharmacology (2005) [Pubmed]
  36. Prostaglandin E2 is a potent regulator of interleukin-12- and interleukin-18-induced natural killer cell interferon-gamma synthesis. Walker, W., Rotondo, D. Immunology (2004) [Pubmed]
  37. Scoparone from Artemisia capillaris inhibits the release of inflammatory mediators in RAW 264.7 cells upon stimulation cells by interferon-gamma Plus LPS. Jang, S., Kim, Y.J., Lee, W.Y., Kwak, K.C., Baek, S.H., Kwak, G.B., Yun, Y.G., Kwon, T.O., Chung, H.T., Chai, K.Y. Arch. Pharm. Res. (2005) [Pubmed]
  38. 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. Chen, B.C., Liao, C.C., Hsu, M.J., Liao, Y.T., Lin, C.C., Sheu, J.R., Lin, C.H. J. Immunol. (2006) [Pubmed]
  39. Role of prostaglandin E2 receptors in migration of murine and human breast cancer cells. Timoshenko, A.V., Xu, G., Chakrabarti, S., Lala, P.K., Chakraborty, C. Exp. Cell Res. (2003) [Pubmed]
  40. Anti-inflammatory effect of two isoforms of COX in H. pylori-induced gastritis in mice: possible involvement of PGE2. Tanigawa, T., Watanabe, T., Hamaguchi, M., Sasaki, E., Tominaga, K., Fujiwara, Y., Oshitani, N., Matsumoto, T., Higuchi, K., Arakawa, T. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  41. Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis. Golijanin, D., Tan, J.Y., Kazior, A., Cohen, E.G., Russo, P., Dalbagni, G., Auborn, K.J., Subbaramaiah, K., Dannenberg, A.J. Clin. Cancer Res. (2004) [Pubmed]
  42. Possible involvement of enhanced prostaglandin E2 production in the photosensitivity in xeroderma pigmentosum group A model mice. Kuwamoto, K., Miyauchi-Hashimoto, H., Tanaka, K., Eguchi, N., Inui, T., Urade, Y., Horio, T. J. Invest. Dermatol. (2000) [Pubmed]
  43. Systemic inflammation induces COX-2 mediated prostaglandin D2 biosynthesis in mice spinal cord. Grill, M., Peskar, B.A., Schuligoi, R., Amann, R. Neuropharmacology (2006) [Pubmed]
  44. Mediation of inflammation by encephalitogenic cells: interferon gamma induction of nitric oxide synthase and cyclooxygenase 2. Misko, T.P., Trotter, J.L., Cross, A.H. J. Neuroimmunol. (1995) [Pubmed]
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