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Gene Review

PTGS2  -  prostaglandin-endoperoxide synthase 2...

Sus scrofa

Synonyms: COX-2, COX2, PGHS-2
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Disease relevance of PGHS-2

  • Pharmacologic modulation of iNOS and COX-2 activity may represent a therapeutic target for pigs with pleuropneumonia [1].
  • OBJECTIVE: To determine the amount of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activity in alveolar macrophages in response to Actinobacillus pleuropneumoniae (APP) by determining nitric oxide (NO) and prostaglandin E2 (PGE2) concentrations [1].
  • BACKGROUND: Ischemia increases levels of prostaglandin H synthase-2 (PGHS-2) in neonatal brain and cerebral vasculature, but effects on the developing visual system are unknown [2].
  • Relationship between NOC/oFQ, dynorphin, and COX-2 activation in impaired NMDA cerebrovasodilation after brain injury [3].
  • We examined whether the selective COX-2 inhibitor NS398 would protect neuronal function after global hypoxia/ischemia (H/I) in piglets [4].

High impact information on PGHS-2

  • Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues [5].
  • Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2 [5].
  • CONCLUSIONS: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2 [5].
  • Both PGHS-1 and PGHS-2 contributed equivalently to light-induced prostaglandin synthesis, as shown after selective PGHS-2 blockers, but mRNA expression of PGHS-1 and 2 was not affected by light [6].
  • Endometrial PTGS1 mRNA expression increased 2- to 3-fold after Day 10 of the estrous cycle and pregnancy, whereas PTGS2 mRNA expression increased 76-fold between Days 5 and 15 of the estrous cycle and pregnancy [7].

Chemical compound and disease context of PGHS-2

  • Indomethacin pretreatment inhibited increases in mRNA and protein for PGHS-2 after ischemia, while 7-NI had little effect on increases in PGHS-2 immunoreactivity [8].
  • COX-2-dependent contracting factors, such as thromboxane, contribute to aberrant pulmonary arterial responses in piglets exposed to 3 days of hypoxia [9].
  • Cyclooxygenase-2 (COX-2) protein was detected immunohistochemically in formalin-fixed, paraffin wax-embedded lung tissues from 15 pigs with naturally occurring pleuropneumonia caused by Actinobacillus pleuropneumoniae [10].
  • Cyclooxygenase-2 (COX-2) was detected and localized in 15 pigs with naturally occurring pleuropneumonia using a 437-base pair digoxigenin-labeled cDNA probe in an in situ hybridization protocol [11].
  • Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter [12].

Biological context of PGHS-2


Anatomical context of PGHS-2

  • Because COX-2 expression is regulated in part by MAPKs, we postulated that MAPK pathways would play an integral role in recovery of injured mucosa [13].
  • Mitogen-activated protein kinases regulate COX-2 and mucosal recovery in ischemic-injured porcine ileum [13].
  • Immunostaining for nNOS displayed a different pattern from PGHS-2 in the hippocampus, and was mainly localized to the granule cell layer of the dentate gyrus and the mossy fiber layer [16].
  • And third, the distribution of nNOS is different from PGHS-2 immunoreactivity in the cerebral cortex, hippocampus, and cerebellum [16].
  • In addition, glial cells associated with microvessels in white matter showed PGHS-2 immunoreactivity [16].

Associations of PGHS-2 with chemical compounds

  • Application of 5 x 10(6) PMNs to the serosal surface of ischemia-injured mucosa significantly enhanced recovery of TER (P < 0.05), an effect that was inhibited by the selective COX-2 inhibitor NS-398 (5 microM) and by an IL-1beta receptor antagonist (0.1 mg/ml) [17].
  • Western blot analysis revealed that SB-203580 inhibited upregulation of COX-2 that was observed in untreated ischemic-injured mucosa, whereas PD-98059 had no effect on COX-2 expression [13].
  • (2) Lipopolysaccharide could up-regulate the expression of some inflammatory mediators in PIMs, including TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, and these up-regulated expression of inflammatory mediators correlated with NF-kappaB activation [18].
  • Our results suggest that NF-kappaB activation in PIMs followed by phagocytizing lipopolysaccharide resulted in the up-regulation of TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, which could be alleviated by dexamethasone [18].
  • Inhibition of iNOS and COX-2 decreased NO and PGE2 production, respectively [1].

Other interactions of PGHS-2


Analytical, diagnostic and therapeutic context of PGHS-2


  1. In vitro effects of Actinobacillus pleuropneumoniae on inducible nitric oxide synthase and cyclooxygenase-2 in porcine alveolar macrophages. Cho, W.S., Chae, C. Am. J. Vet. Res. (2003) [Pubmed]
  2. Ischemia increases prostaglandin H synthase-2 levels in retina and visual cortex in piglets. Dégi, R., Thore, C., Bari, F., Thrikawala, N., Nógrádi, A., Robins, G., Domoki, F., Beasley, T.C., Busija, D.W. Graefes Arch. Clin. Exp. Ophthalmol. (2001) [Pubmed]
  3. Relationship between NOC/oFQ, dynorphin, and COX-2 activation in impaired NMDA cerebrovasodilation after brain injury. Kulkarni, M., Armstead, W.M. J. Neurotrauma (2002) [Pubmed]
  4. Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets. Domoki, F., Perciaccante, J.V., Puskar, M., Bari, F., Busija, D.W. Neuroreport (2001) [Pubmed]
  5. Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2. Blikslager, A.T., Zimmel, D.N., Young, K.M., Campbell, N.B., Little, D., Argenzio, R.A. Gut (2002) [Pubmed]
  6. Light induces peroxidation in retina by activating prostaglandin G/H synthase. Hanna, N., Peri, K.G., Abran, D., Hardy, P., Doke, A., Lachapelle, P., Roy, M.S., Orquin, J., Varma, D.R., Chemtob, S. Free Radic. Biol. Med. (1997) [Pubmed]
  7. Expression of porcine endometrial prostaglandin synthase during the estrous cycle and early pregnancy, and following endocrine disruption of pregnancy. Ashworth, M.D., Ross, J.W., Hu, J., White, F.J., Stein, D.R., Desilva, U., Johnson, G.A., Spencer, T.E., Geisert, R.D. Biol. Reprod. (2006) [Pubmed]
  8. Effects of anoxic stress on prostaglandin H synthase isoforms in piglet brain. Dégì, R., Bari, F., Thrikawala, N., Beasley, T.C., Thore, C., Louis, T.M., Busija, D.W. Brain Res. Dev. Brain Res. (1998) [Pubmed]
  9. Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs. Fike, C.D., Kaplowitz, M.R., Zhang, Y., Pfister, S.L. J. Appl. Physiol. (2005) [Pubmed]
  10. Immunohistochemical detection of cyclooxygenase-2 in lungs of pigs naturally infected with Actinobacillus pleuropneumoniae. Cho, W.S., Chae, C. J. Comp. Pathol. (2002) [Pubmed]
  11. Expression of cyclooxygenase-2 in swine naturally infected with Actinobacillus pleuropneumoniae. Cho, W.S., Chae, C. Vet. Pathol. (2003) [Pubmed]
  12. Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. Mastrangelo, D., Wisard, M., Rohner, S., Leisinger, H., Iselin, C.E. Urol. Res. (2000) [Pubmed]
  13. Mitogen-activated protein kinases regulate COX-2 and mucosal recovery in ischemic-injured porcine ileum. Shifflett, D.E., Jones, S.L., Moeser, A.J., Blikslager, A.T. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  14. Candidate gene analysis for loci affecting litter size and ovulation rate in swine. Linville, R.C., Pomp, D., Johnson, R.K., Rothschild, M.F. J. Anim. Sci. (2001) [Pubmed]
  15. Increased pulmonary vascular contraction to serotonin after cardiopulmonary bypass: role of cyclooxygenase. Sato, K., Li, J., Metais, C., Bianchi, C., Sellke, F. J. Surg. Res. (2000) [Pubmed]
  16. Regional distribution of prostaglandin H synthase-2 and neuronal nitric oxide synthase in piglet brain. Dégì, R., Bari, F., Beasley, T.C., Thrikawala, N., Thore, C., Louis, T.M., Busija, D.W. Pediatr. Res. (1998) [Pubmed]
  17. Neutrophils augment recovery of porcine ischemia-injured ileal mucosa by an IL-1beta- and COX-2-dependent mechanism. Shifflett, D.E., Bottone, F.G., Young, K.M., Moeser, A.J., Jones, S.L., Blikslager, A.T. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  18. LPS induces pulmonary intravascular macrophages producing inflammatory mediators via activating NF-kappaB. Chen, Z.T., Li, S.L., Cai, E.Q., Wu, W.L., Jin, J.S., Zhu, B. J. Cell. Biochem. (2003) [Pubmed]
  19. Interleukin-1beta activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon. Tjwa, E.T., Bradley, J.M., Keenan, C.M., Kroese, A.B., Sharkey, K.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  20. Arachidonic acid metabolites and an early stage of pulmonary hypertension in chronically hypoxic newborn pigs. Fike, C.D., Kaplowitz, M.R., Pfister, S.L. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  21. Prostaglandin f(2alpha) induces distinct physiological responses in porcine corpora lutea after acquisition of luteolytic capacity. Diaz, F.J., Crenshaw, T.D., Wiltbank, M.C. Biol. Reprod. (2000) [Pubmed]
  22. Aspirin, but not the more selective cyclooxygenase (COX)-2 inhibitors meloxicam and SC 58125, aggravates postischaemic cardiac dysfunction, independent of COX function. Heindl, B., Becker, B.F. Naunyn Schmiedebergs Arch. Pharmacol. (2001) [Pubmed]
  23. Induction of cyclooxygenase-2 following anoxic stress in piglet cerebral arteries. Busija, D.W., Thore, C., Beasley, T., Bari, F. Microcirculation (New York, N.Y. : 1994) (1996) [Pubmed]
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