cyclooxygenase 2


Gene Symbol: cyclooxygenase 2
Description: prostaglandin-endoperoxide synthase 2
Alias: COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2, Pghs2, TIS10, gripghs, prostaglandin G/H synthase 2, PGH synthase 2, cyclooxygenase-2, glucocorticoid-regulated inflammatory cyclooxygenase, macrophage activation-associated marker protein P71/73, prostaglandin H2 synthase 2
Species: mouse
Products:     cyclooxygenase 2

Top Publications

  1. Ishikawa T, Oshima M, Herschman H. Cox-2 deletion in myeloid and endothelial cells, but not in epithelial cells, exacerbates murine colitis. Carcinogenesis. 2011;32:417-26 pubmed publisher
    ..These results suggest that COX-2 expression in myeloid cells and endothelial cells, but not epithelial cells, is important for protection of epithelial cells in this murine colitis model. ..
  2. Lee S, Na S, Heo J, Kim M, Kim Y, Lee M, et al. Arachidonic acid release by H2O2 mediated proliferation of mouse embryonic stem cells: involvement of Ca2+/PKC and MAPKs-induced EGFR transactivation. J Cell Biochem. 2009;106:787-97 pubmed publisher
    ..In conclusion, H(2)O(2) increased AA release and PGE(2) production by the upregulation of cPLA(2) and COX-2 via Ca(2+)/PKC/MAPKs and EGFR transactivation, subsequently proliferation of mouse ES cells. ..
  3. Li Q, Guo Y, Tan W, Ou Q, Wu W, Sturza D, et al. Cardioprotection afforded by inducible nitric oxide synthase gene therapy is mediated by cyclooxygenase-2 via a nuclear factor-kappaB dependent pathway. Circulation. 2007;116:1577-84 pubmed
    ..Thus, iNOS imparts its protective effects, at least in part, by recruiting NF-kappaB, leading to COX-2 upregulation. However, COX-2 does not play an important cardioprotective role under basal conditions (when iNOS is not upregulated). ..
  4. Kanayama M, Yamaguchi S, Shibata T, Shibata N, Kobayashi M, Nagai R, et al. Identification of a serum component that regulates cyclooxygenase-2 gene expression in cooperation with 4-hydroxy-2-nonenal. J Biol Chem. 2007;282:24166-74 pubmed
    ..These findings represent a demonstration of a link between lipoprotein modification and activation of the inflammatory potential of macrophages. ..
  5. Xu M, Choudhary S, Voznesensky O, Gao Q, Adams D, Diaz Doran V, et al. Basal bone phenotype and increased anabolic responses to intermittent parathyroid hormone in healthy male COX-2 knockout mice. Bone. 2010;47:341-52 pubmed publisher
    ..It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. ..
  6. Shim M, Foley J, Anna C, Mishina Y, Eling T. Embryonic expression of cyclooxygenase-2 causes malformations in axial skeleton. J Biol Chem. 2010;285:16206-17 pubmed publisher
    ..Our results demonstrate that the aberrant COX-2 signaling during embryonic development is teratogenic and suggest a possible association of COX-2 with fetal malformations of unknown etiology. ..
  7. Narasimha A, Watanabe J, Ishikawa T, Priceman S, Wu L, Herschman H, et al. Absence of myeloid COX-2 attenuates acute inflammation but does not influence development of atherosclerosis in apolipoprotein E null mice. Arterioscler Thromb Vasc Biol. 2010;30:260-8 pubmed publisher
    ..Our results suggest that COX-2 expression in myeloid cells, including macrophages, does not influence the development of atherosclerosis in mice. ..
  8. Fong L, Jiang Y, Riley M, Liu X, Smalley K, Guttridge D, et al. Prevention of upper aerodigestive tract cancer in zinc-deficient rodents: inefficacy of genetic or pharmacological disruption of COX-2. Int J Cancer. 2008;122:978-89 pubmed
    ..Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. ..
  9. Hamada T, Tsuchihashi S, Avanesyan A, Duarte S, Moore C, Busuttil R, et al. Cyclooxygenase-2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/reperfusion injury. J Immunol. 2008;180:1843-53 pubmed
    ..The data also suggest that potential valuable therapeutic approaches in liver I/R injury may result from further studies aimed at identifying specific COX-2-derived prostanoid pathways. ..

More Information


  1. Choudhary S, Blackwell K, Voznesensky O, Deb Roy A, Pilbeam C. Prostaglandin E2 acts via bone marrow macrophages to block PTH-stimulated osteoblast differentiation in vitro. Bone. 2013;56:31-41 pubmed publisher
    ..This suppression of OB differentiation could contribute to the bone loss seen with continuous PTH in vivo...
  2. Aid S, Langenbach R, Bosetti F. Neuroinflammatory response to lipopolysaccharide is exacerbated in mice genetically deficient in cyclooxygenase-2. J Neuroinflammation. 2008;5:17 pubmed publisher
    ..These results show that inhibiting COX-2 activity can exacerbate the inflammatory response to LPS, possibly by increasing glial cells activation and upregulating the STAT3 and SOCS3 pathways in the brain. ..
  3. Kirkby N, Lundberg M, Harrington L, Leadbeater P, Milne G, Potter C, et al. Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system. Proc Natl Acad Sci U S A. 2012;109:17597-602 pubmed publisher
  4. Toscano C, Ueda Y, Tomita Y, Vicini S, Bosetti F. Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice. Brain Res Bull. 2008;75:598-609 pubmed publisher
    ..Our results suggest that PTGS-2 activity and its specific products may modulate neuronal excitability by affecting GABAergic neurotransmission. Further, inhibition of PTGS-2, but not PTGS-1, may increase the susceptibility to seizures. ..
  5. Cathcart M, Tamosiuniene R, Chen G, Neilan T, Bradford A, O Byrne K, et al. Cyclooxygenase-2-linked attenuation of hypoxia-induced pulmonary hypertension and intravascular thrombosis. J Pharmacol Exp Ther. 2008;326:51-8 pubmed publisher
    ..The data provide evidence that endogenous prostaglandins modulate the pulmonary response to hypoxia. ..
  6. Xie C, Ming X, Wang Q, Schwarz E, Guldberg R, O Keefe R, et al. COX-2 from the injury milieu is critical for the initiation of periosteal progenitor cell mediated bone healing. Bone. 2008;43:1075-83 pubmed publisher
    ..Elimination of COX-2 at the early stage of healing could lead to detrimental effects on periosteal progenitor cell-initiated cortical bone repair. ..
  7. Naik A, Xie C, Zuscik M, Kingsley P, Schwarz E, Awad H, et al. Reduced COX-2 expression in aged mice is associated with impaired fracture healing. J Bone Miner Res. 2009;24:251-64 pubmed publisher
    The cellular and molecular events responsible for reduced fracture healing with aging are unknown. Cyclooxygenase 2 (COX-2), the inducible regulator of prostaglandin E(2) (PGE(2)) synthesis, is critical for normal bone repair...
  8. Parazzoli S, Harmon J, VALLERIE S, Zhang T, Zhou H, Robertson R. Cyclooxygenase-2, not microsomal prostaglandin E synthase-1, is the mechanism for interleukin-1?-induced prostaglandin E2 production and inhibition of insulin secretion in pancreatic islets. J Biol Chem. 2012;287:32246-53 pubmed publisher
    ..IL-1? inhibited glucose-stimulated insulin secretion equally in both WT and mPGES-1(-/-) islets, indicating that COX-2, not mPGES-1, mediates IL-1?-induced PGE(2) production and subsequent inhibition of insulin secretion. ..
  9. Yoon Y, Lee Y, Choi J, Cho M, Kang J. Coordinated induction of cyclooxygenase-2/prostaglandin E2 and hepatocyte growth factor by apoptotic cells prevents lung fibrosis. J Leukoc Biol. 2013;94:1037-49 pubmed publisher
    ..Up-regulation of COX-2/PGE2 and HGF through a positive-feedback loop may be an important mechanism whereby apoptotic cell instillation exerts the net results of anti-inflammatory, antiapoptotic, and antifibrotic action. ..
  10. Chan M, Moore A. Resolution of inflammation in murine autoimmune arthritis is disrupted by cyclooxygenase-2 inhibition and restored by prostaglandin E2-mediated lipoxin A4 production. J Immunol. 2010;184:6418-26 pubmed publisher
    ..These findings may explain the enigma regarding why COX-2 inhibitors are palliative rather than curative in humans, because blocking resolution may mitigate the benefit of preventing induction. ..
  11. Hu M, Peluffo G, Chen H, Gelman R, Schnitt S, Polyak K. Role of COX-2 in epithelial-stromal cell interactions and progression of ductal carcinoma in situ of the breast. Proc Natl Acad Sci U S A. 2009;106:3372-7 pubmed publisher
  12. Ishikawa T, Jain N, Herschman H. Feedback regulation of cyclooxygenase-2 transcription ex vivo and in vivo. Biochem Biophys Res Commun. 2009;378:534-8 pubmed publisher
    ..Our results suggest Cox-2 expression is regulated by cell type specific feedback mechanisms, both in cultured cells and in living animals. ..
  13. Wang D, Patel V, Ricciotti E, Zhou R, Levin M, Gao E, et al. Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function. Proc Natl Acad Sci U S A. 2009;106:7548-52 pubmed publisher
    ..Inhibition of COX-2 in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of COX-2. ..
  14. Fredenburgh L, Velandia M, Ma J, Olszak T, Cernadas M, Englert J, et al. Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased mortality during polymicrobial sepsis. J Immunol. 2011;187:5255-67 pubmed publisher
    ..Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis...
  15. Kirkby N, Zaiss A, Wright W, Jiao J, Chan M, Warner T, et al. Differential COX-2 induction by viral and bacterial PAMPs: Consequences for cytokine and interferon responses and implications for anti-viral COX-2 directed therapies. Biochem Biophys Res Commun. 2013;438:249-56 pubmed publisher
    b>Cyclooxygenase 2 (COX)-2 is induced by bacterial and viral infections and has complex, poorly understood roles in anti-pathogen immunity...
  16. Xie C, Liang B, Xue M, Lin A, Loiselle A, Schwarz E, et al. Rescue of impaired fracture healing in COX-2-/- mice via activation of prostaglandin E2 receptor subtype 4. Am J Pathol. 2009;175:772-85 pubmed publisher
    ..Taken together, our studies demonstrate that EP2 and EP4 have differential functions during endochondral bone repair. Activation of EP4, but not EP2 rescued impaired bone fracture healing in COX-2(-/-) mice...
  17. Seta F, Chung A, Turner P, Mewburn J, Yu Y, Funk C. Renal and cardiovascular characterization of COX-2 knockdown mice. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1751-60 pubmed publisher
    ..COX-2(Neo/Neo) mice, therefore, provide a genetic surrogate of coxib therapy with disrupted prostacyclin biosynthesis that predisposes to induced arterial thrombosis. ..
  18. Colby J, Klein R, McArthur M, Conti C, Kiguchi K, Kawamoto T, et al. Progressive metaplastic and dysplastic changes in mouse pancreas induced by cyclooxygenase-2 overexpression. Neoplasia. 2008;10:782-96 pubmed
    ..The progressive nature of the metaplastic/dysplastic changes observed in this model make it a valuable tool for examining the transition from chronic inflammation to neoplasia. ..
  19. Baglole C, Maggirwar S, Gasiewicz T, Thatcher T, Phipps R, Sime P. The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-kappaB family member RelB. J Biol Chem. 2008;283:28944-57 pubmed publisher
    ..The association between RelB and AhR may represent a new therapeutic and more selective target with which to combat inflammation-associated diseases. ..
  20. Barbieri S, Amadio P, Gianellini S, Tarantino E, Zacchi E, Veglia F, et al. Cyclooxygenase-2-derived prostacyclin regulates arterial thrombus formation by suppressing tissue factor in a sirtuin-1-dependent-manner. Circulation. 2012;126:1373-84 pubmed publisher
  21. Fredenburgh L, Liang O, Macias A, Polte T, Liu X, Riascos D, et al. Absence of cyclooxygenase-2 exacerbates hypoxia-induced pulmonary hypertension and enhances contractility of vascular smooth muscle cells. Circulation. 2008;117:2114-22 pubmed publisher
    ..COX-2-deficient PASMCs have a maladaptive response to hypoxia manifested by exaggerated contractility, which may be rescued by either COX-2-derived prostaglandin I(2) or prostaglandin E(2). ..
  22. Moses T, Wagner L, Fleming S. TLR4-mediated Cox-2 expression increases intestinal ischemia/reperfusion-induced damage. J Leukoc Biol. 2009;86:971-80 pubmed publisher
    ..Together, these data indicate that TLR4 stimulation of Cox-2 activation of PGE2 production is necessary but not sufficient for intestinal IR-induced damage and inflammation. ..
  23. Kim J, Park S, Yun K, Cho Y, Park H, Lee K. Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-kappaB in RAW 264.7 macrophages. Eur J Pharmacol. 2008;584:175-84 pubmed publisher
    ..These results suggest that the anti-inflammatory properties of ILG are caused by iNOS, COX-2, TNF-alpha, and IL-6 down-regulation due to NF-kappaB inhibition via the suppression of IKK, ERK1/2 and p38 phosphorylation in RAW 264.7 cells...
  24. Ahmad M, Rose M, Vagni V, Griffith R, Dixon C, Kochanek P, et al. Genetic disruption of cyclooxygenase-2 does not improve histological or behavioral outcome after traumatic brain injury in mice. J Neurosci Res. 2008;86:3605-12 pubmed publisher
    ..COX-2 gene disruption did not alter Morris water maze performance. Taken together, these results suggest only a minor role for COX-2 activity in determining outcome after TBI in mouse. ..
  25. Papanicolaou K, Streicher J, Ishikawa T, Herschman H, Wang Y, Walsh K. Preserved heart function and maintained response to cardiac stresses in a genetic model of cardiomyocyte-targeted deficiency of cyclooxygenase-2. J Mol Cell Cardiol. 2010;49:196-209 pubmed publisher
    ..In conclusion, our animal-based analyses together with the cell-based observations portray a limited role of cardiomyocyte-produced Cox-2 at baseline and in the context of ischemic or hemodynamic challenge. ..
  26. Narasimha A, Watanabe J, Lin J, Hama S, Langenbach R, Navab M, et al. A novel anti-atherogenic role for COX-2--potential mechanism for the cardiovascular side effects of COX-2 inhibitors. Prostaglandins Other Lipid Mediat. 2007;84:24-33 pubmed
    ..Our results suggest, for the first time, that COX-2 deficiency contributes to the pro-atherogenic properties of HDL in mice. ..
  27. Hui Y, Ricciotti E, Crichton I, Yu Z, Wang D, Stubbe J, et al. Targeted deletions of cyclooxygenase-2 and atherogenesis in mice. Circulation. 2010;121:2654-60 pubmed publisher
    ..TC COX-2 does not detectably influence TC development or function or atherogenesis in mice. ..
  28. Díaz Muñoz M, Osma García I, Fresno M, Iñiguez M. Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages. Biochem J. 2012;443:451-61 pubmed publisher
    ..the involvement of PGE receptors [EPs (E-prostanoids)] showed that incubation with EP2 agonists up-regulated both COX2 and mPGES-1 mRNA levels...
  29. Yu Z, Crichton I, Tang S, Hui Y, Ricciotti E, Levin M, et al. Disruption of the 5-lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice. Proc Natl Acad Sci U S A. 2012;109:6727-32 pubmed publisher
    Suppression of cyclooxygenase 2 (COX-2)-derived prostacyclin (PGI(2)) is sufficient to explain most elements of the cardiovascular hazard from nonsteroidal antinflammatory drugs (NSAIDs)...
  30. Kirkby N, Zaiss A, Urquhart P, Jiao J, Austin P, Al Yamani M, et al. LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression. PLoS ONE. 2013;8:e69524 pubmed publisher
    ..In addition, we determined expression from the Cox2 gene using a knockin reporter mouse in which luciferase activity reflects Cox2 gene expression...
  31. Morham S, Langenbach R, Loftin C, Tiano H, Vouloumanos N, Jennette J, et al. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell. 1995;83:473-82 pubmed
    The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is induced at high levels in migratory and other responding cells by pro-inflammatory stimuli. COX-2 is generally considered to be a mediator of inflammation...
  32. Loftin C, Trivedi D, Langenbach R. Cyclooxygenase-1-selective inhibition prolongs gestation in mice without adverse effects on the ductus arteriosus. J Clin Invest. 2002;110:549-57 pubmed
    ..Therefore, COX-1-selective inhibitors may provide effective treatment to delay preterm labor with fewer adverse effects on fetal or neonatal health than nonselective or COX-2-selective inhibitors. ..
  33. Leu T, Charoenfuprasert S, Yen C, Fan C, Maa M. Lipopolysaccharide-induced c-Src expression plays a role in nitric oxide and TNFalpha secretion in macrophages. Mol Immunol. 2006;43:308-16 pubmed
    ..7 and animal models of sepsis greatly suppresses TNFalpha secretion and serum TNFalpha level, respectively. Therefore, we conclude that c-Src, with its LPS induction, has an unperceived role in transmitting LPS signaling in macrophages. ..
  34. Morteau O, Morham S, Sellon R, Dieleman L, Langenbach R, Smithies O, et al. Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2. J Clin Invest. 2000;105:469-78 pubmed
  35. Chikazu D, Li X, Kawaguchi H, Sakuma Y, Voznesensky O, Adams D, et al. Bone morphogenetic protein 2 induces cyclo-oxygenase 2 in osteoblasts via a Cbfal binding site: role in effects of bone morphogenetic protein 2 in vitro and in vivo. J Bone Miner Res. 2002;17:1430-40 pubmed
  36. Xuan Y, Guo Y, Zhu Y, Wang O, Rokosh G, Messing R, et al. Role of the protein kinase C-epsilon-Raf-1-MEK-1/2-p44/42 MAPK signaling cascade in the activation of signal transducers and activators of transcription 1 and 3 and induction of cyclooxygenase-2 after ischemic preconditioning. Circulation. 2005;112:1971-8 pubmed
  37. Rao J, Langenbach R, Bosetti F. Down-regulation of brain nuclear factor-kappa B pathway in the cyclooxygenase-2 knockout mouse. Brain Res Mol Brain Res. 2005;139:217-24 pubmed
    ..Overall, our data indicate that constitutive brain NF-kappaB activity is decreased in COX-2 deficient mice and suggest a reciprocal coupling between NF-kappaB and COX-2. ..
  38. Muthian G, Raikwar H, Johnson C, Rajasingh J, Kalgutkar A, Marnett L, et al. COX-2 inhibitors modulate IL-12 signaling through JAK-STAT pathway leading to Th1 response in experimental allergic encephalomyelitis. J Clin Immunol. 2006;26:73-85 pubmed
  39. Tiano H, Loftin C, Akunda J, Lee C, Spalding J, Sessoms A, et al. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res. 2002;62:3395-401 pubmed
    ..Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation. ..
  40. Han X, Chen S, Sun Y, Nadler J, Bleich D. Induction of cyclooxygenase-2 gene in pancreatic beta-cells by 12-lipoxygenase pathway product 12-hydroxyeicosatetraenoic acid. Mol Endocrinol. 2002;16:2145-54 pubmed
    ..These data demonstrate that 12-HETE mediates cytokine-induced COX-2 gene transcription and resultant PGE2 production in pancreatic beta-cells. ..
  41. Robertson G, Xie C, Chen D, Awad H, Schwarz E, O Keefe R, et al. Alteration of femoral bone morphology and density in COX-2-/- mice. Bone. 2006;39:767-72 pubmed
    ..In conclusion, our study suggests that genetic ablation of COX-2 may have a sex-related effect on cortical bone homeostasis and COX-2 plays a role in maintaining normal bone micro-architecture and density in mice. ..
  42. Ejima K, Layne M, Carvajal I, Kritek P, Baron R, Chen Y, et al. Cyclooxygenase-2-deficient mice are resistant to endotoxin-induced inflammation and death. FASEB J. 2003;17:1325-7 pubmed
    ..These beneficial effects occur, in part, by a compensatory increase in IL-10 that counterbalances the pro-inflammatory host response to endotoxemia. ..
  43. Hunot S, Vila M, Teismann P, Davis R, Hirsch E, Przedborski S, et al. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101:665-70 pubmed
    ..Our data revealed that JNK2- and JNK3-induced COX-2 may be a principle pathway responsible for neurodegeneration in PD. ..
  44. Fukata M, Chen A, Klepper A, Krishnareddy S, Vamadevan A, Thomas L, et al. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: Role in proliferation and apoptosis in the intestine. Gastroenterology. 2006;131:862-77 pubmed
    ..We wished to test the hypothesis that cyclooxygenase 2 (Cox-2)-derived prostaglandin E2 (PGE2) is important in TLR4-related mucosal repair...
  45. Chen C, Magee J, Bazan N. Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity. J Neurophysiol. 2002;87:2851-7 pubmed
    ..Our results indicate that COX-2-generated PGE2 regulates membrane excitability and long-term synaptic plasticity in hippocampal perforant path-dentate gyrus synapses...
  46. Cao Y, Prescott S. Many actions of cyclooxygenase-2 in cellular dynamics and in cancer. J Cell Physiol. 2002;190:279-86 pubmed
    ..Inhibition of COX-2 promises to be an effective approach in the prevention and treatment of cancer, especially colorectal cancer. ..
  47. Iadecola C, Niwa K, Nogawa S, Zhao X, Nagayama M, Araki E, et al. Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci U S A. 2001;98:1294-9 pubmed
    ..Thus, COX-2 is involved in pathogenic events occurring in both the early and late stages of cerebral ischemia and may be a valuable therapeutic target for treatment of human stroke. ..
  48. Yang T, Endo Y, Huang Y, Smart A, Briggs J, Schnermann J. Renin expression in COX-2-knockout mice on normal or low-salt diets. Am J Physiol Renal Physiol. 2000;279:F819-25 pubmed
  49. Langenbach R, Loftin C, Lee C, Tiano H. Cyclooxygenase-deficient mice. A summary of their characteristics and susceptibilities to inflammation and carcinogenesis. Ann N Y Acad Sci. 1999;889:52-61 pubmed
    ..Furthermore, data from COX-deficient mice indicate that both isoforms can contribute to the inflammatory response and that both isoforms have significant roles in carcinogenesis. ..
  50. Murakami M, Nakashima K, Kamei D, Masuda S, Ishikawa Y, Ishii T, et al. Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2. J Biol Chem. 2003;278:37937-47 pubmed
    ..Collectively, mPGES-2 is a unique PGES that can be coupled with both COXs and may play a role in the production of the PGE2 involved in both tissue homeostasis and disease. ..
  51. Kirtikara K, Morham S, Raghow R, Laulederkind S, Kanekura T, Goorha S, et al. Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells. J Exp Med. 1998;187:517-23 pubmed immortalized, nontransformed cells derived from wild-type, cyclooxygenase 1-deficient (COX-1(-/-)) or cyclooxygenase 2-deficient (COX-2(-/-)) mice was examined after treatment with interleukin (IL)-1beta, tumor necrosis factor ..
  52. Rocca B, Spain L, Pure E, Langenbach R, Patrono C, Fitzgerald G. Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development. J Clin Invest. 1999;103:1469-77 pubmed
    ..COX-dependent PG generation may represent a mechanism of thymic stromal support for T-cell development. ..
  53. Kurumbail R, Stevens A, Gierse J, McDonald J, Stegeman R, Pak J, et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996;384:644-8 pubmed
    ..0 to 2.5 A resolution. These structures explain the structural basis for the selective inhibition of COX-2, and demonstrate some of the conformational changes associated with time-dependent inhibition. ..
  54. Kawano T, Anrather J, Zhou P, Park L, Wang G, Frys K, et al. Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity. Nat Med. 2006;12:225-9 pubmed
    ..An EP1 receptor inhibitor reduces brain injury when administered 6 hours after MCA occlusion, suggesting that EP1 receptor inhibition may be a viable therapeutic option in ischemic stroke. ..
  55. Okada Y, Lorenzo J, Freeman A, Tomita M, Morham S, Raisz L, et al. Prostaglandin G/H synthase-2 is required for maximal formation of osteoclast-like cells in culture. J Clin Invest. 2000;105:823-32 pubmed
    ..Mice lacking PGHS-1 were similar to wild-type mice in all of these parameters. These data suggest that PGHS-2 is not necessary for wild-type bone development but plays a critical role in bone resorption stimulated by 1,25-D and PTH. ..
  56. Bonner J, Rice A, Ingram J, Moomaw C, Nyska A, Bradbury A, et al. Susceptibility of cyclooxygenase-2-deficient mice to pulmonary fibrogenesis. Am J Pathol. 2002;161:459-70 pubmed
    ..These findings indicate that the COX-2 enzyme is protective against pulmonary fibrogenesis, and we suggest that COX-2 generation of PGE(2) is an important factor in resolving inflammation...
  57. Xiang Z, Ho L, Yemul S, Zhao Z, Qing W, Pompl P, et al. Cyclooxygenase-2 promotes amyloid plaque deposition in a mouse model of Alzheimer's disease neuropathology. Gene Expr. 2002;10:271-8 pubmed
    ..Collectively these data suggest that COX-2 influences APP processing and promotes amyloidosis in the brain. ..
  58. Egan K, Lawson J, Fries S, Koller B, Rader D, Smyth E, et al. COX-2-derived prostacyclin confers atheroprotection on female mice. Science. 2004;306:1954-7 pubmed
    ..receptor subtype alpha to up-regulate the production of atheroprotective prostacyclin, PGI2, by activation of cyclooxygenase 2 (COX-2)...
  59. Dinchuk J, Car B, Focht R, Johnston J, Jaffee B, Covington M, et al. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature. 1995;378:406-9 pubmed
    ..Female Cox-2-/- mice were infertile. COX-2 deficiency failed to alter inflammatory responses in several standard models, but striking mitigation of endotoxin-induced hepatocellular cytotoxicity was observed. ..
  60. Basselin M, Villacreses N, Langenbach R, Ma K, Bell J, Rapoport S. Resting and arecoline-stimulated brain metabolism and signaling involving arachidonic acid are altered in the cyclooxygenase-2 knockout mouse. J Neurochem. 2006;96:669-79 pubmed
    ..This response likely reflects selective COX-2-mediated conversion of PLA2-released AA to prostanoids. ..
  61. Xu Z, Choudhary S, Voznesensky O, Mehrotra M, Woodard M, Hansen M, et al. Overexpression of COX-2 in human osteosarcoma cells decreases proliferation and increases apoptosis. Cancer Res. 2006;66:6657-64 pubmed
  62. Bosetti F, Weerasinghe G. The expression of brain cyclooxygenase-2 is down-regulated in the cytosolic phospholipase A2 knockout mouse. J Neurochem. 2003;87:1471-7 pubmed
    ..This suggests that cPLA2 is critical for COX-2-derived eicosanoid production in mouse brain. ..
  63. Lama V, Moore B, Christensen P, Toews G, Peters Golden M. Prostaglandin E2 synthesis and suppression of fibroblast proliferation by alveolar epithelial cells is cyclooxygenase-2-dependent. Am J Respir Cell Mol Biol. 2002;27:752-8 pubmed
    ..These alterations in AEC phenotype likely contribute to the propensity for pulmonary fibrosis observed in COX-2-deficient mice. ..
  64. Zhang X, Schwarz E, Young D, Puzas J, Rosier R, O Keefe R. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest. 2002;109:1405-15 pubmed
    ..These results provide a model whereby COX-2 regulates the induction of cbfa1 and osterix to mediate normal skeletal repair. ..
  65. Loftin C, Trivedi D, Tiano H, Clark J, Lee C, Epstein J, et al. Failure of ductus arteriosus closure and remodeling in neonatal mice deficient in cyclooxygenase-1 and cyclooxygenase-2. Proc Natl Acad Sci U S A. 2001;98:1059-64 pubmed
    ..Together, these data establish roles for COX-1, and especially for COX-2, in the transition of the cardiopulmonary circulation at birth. ..
  66. Chulada P, Thompson M, Mahler J, Doyle C, Gaul B, Lee C, et al. Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res. 2000;60:4705-8 pubmed
    ..The results indicate that COX-1, as well as COX-2, plays a key role in intestinal tumorigenesis and that COX-1 may also be a chemotherapeutic target for nonsteroidal anti-inflammatory drugs. ..
  67. Williams C, Mann M, DuBois R. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 1999;18:7908-16 pubmed
    ..The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/ or immune function. ..
  68. Kawaguchi H, Raisz L, Voznesensky O, Alander C, Hakeda Y, Pilbeam C. Regulation of the two prostaglandin G/H synthases by parathyroid hormone, interleukin-1, cortisol, and prostaglandin E2 in cultured neonatal mouse calvariae. Endocrinology. 1994;135:1157-64 pubmed
  69. Yu Y, Fan J, Chen X, Wang D, Klein Szanto A, Campbell R, et al. Genetic model of selective COX2 inhibition reveals novel heterodimer signaling. Nat Med. 2006;12:699-704 pubmed
    ..These drugs block the cyclooxygenase activity of prostaglandin H synthase-2 (PGHS2), but do not affect the associated peroxidase function...
  70. Han S, Lee N, Kim K, Jang I, Yim M, Kim J, et al. Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis. Blood. 2005;106:1240-5 pubmed
    ..This inhibition can be rescued by the addition of exogenous PGE2, suggesting that COX-2-dependent PGE2 induction by RANKL in osteoclast precursors is required for osteoclast differentiation. ..
  71. Seno H, Oshima M, Ishikawa T, Oshima H, Takaku K, Chiba T, et al. Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polyps. Cancer Res. 2002;62:506-11 pubmed
  72. Li S, Wang Y, Matsumura K, Ballou L, Morham S, Blatteis C. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2(-/-), but not in cyclooxygenase-1(-/-) mice. Brain Res. 1999;825:86-94 pubmed
    ..By contrast, COX-2+/- and COX-2-/- mice displayed no Tc rise after LPS. PFS did not affect the Tc of any animal. It would appear therefore that COX-2 is necessary for LPS-induced fever production. ..