Genomes and Genes
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
Products: cyclooxygenase 2
- 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. ..
- 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. ..
- 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). ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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 publisherThe 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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 publisherb>Cyclooxygenase 2 (COX)-2 is induced by bacterial and viral infections and has complex, poorly understood roles in anti-pathogen immunity...
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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). ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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 publisherSuppression of cyclooxygenase 2 (COX-2)-derived prostacyclin (PGI(2)) is sufficient to explain most elements of the cardiovascular hazard from nonsteroidal antinflammatory drugs (NSAIDs)...
- 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...
- 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. ..
- 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. ..
- 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
- 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
- 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
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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...
- 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. ..
- 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
- 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. ..
- 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. ..
- 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..in 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 ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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)...
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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...
- 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. ..
- 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
- 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. ..