ライフサイエンスコーパス: mPGES-1

1 mPGES-1 -/- mice developed severe and progressive hypert

2 mPGES-1 -/- mice exhibited a remarkable inhibition of hi

3 mPGES-1 activation, PGE2 production, and edema formation

4 mPGES-1 deficient mice also exhibited attenuation of mec

5 mPGES-1 deletion augmented expression of both prostacycl

6 mPGES-1 inhibited the expression of phosphatase and tens

7 mPGES-1 is a promising target for development of new ant

8 mPGES-1 is overexpressed in human cholangiocarcinoma tis

9 mPGES-1 is widely considered to be the final enzyme regu

10 mPGES-1 null and heterozygous mice exhibited decreased i

11 mPGES-1 promotes experimental cholangiocarcinogenesis an

12 mPGES-1(-/-) LDLR(-/-) plaques were enriched with fibril

13 mPGES-1-derived PGE(2) accelerates atherogenesis in LDLR

14 mPGES-1-expressing cells in tumors from different subtyp

15 mPGES-1-mediated inhibition of PTEN is regulated through

16 ucible COX-2 and microsomal PGE2 synthase 1 (mPGES-1) (1).

17 mice deficient in microsomal PGE synthase 1 (mPGES-1) and in the receptors for PGI2.

18 rs of microsomal prostaglandin E synthase 1 (mPGES-1) are in the early phase of clinical development.

19 on of microsomal prostaglandin E synthase 1 (mPGES-1) confers analgesia, attenuates atherogenesis, an

20 tion in microsomal prostaglandin synthase 1 (mPGES-1) expression.

21 on of microsomal prostaglandin E synthase 1 (mPGES-1) in mice attenuates the response to vascular inj

22 Microsomal prostaglandin E synthase 1 (mPGES-1) is a key enzyme of the arachidonic acid cascade

23 Microsomal prostaglandin E(2) synthase 1 (mPGES-1) is a promising target for treating inflammatory

24 Microsomal prostaglandin E synthase 1 (mPGES-1) is an alpha-helical homotrimeric integral membr

25 Microsomal prostaglandin E2 synthase 1 (mPGES-1) is recognized as a promising target for a next

26 OX-2, microsomal prostaglandin E synthase 1 (mPGES-1), and EP receptors, was assessed at baseline and

27 minal synthase microsomal PGE(2) synthase 1 (mPGES-1), which is responsible for generating PGE(2), in

28 ) and microsomal prostaglandin E synthase 1 (mPGES-1).

29 n of microsomal prostaglandin E2 synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO) is currently pursued

30 ls of microsomal prostaglandin E synthase-1 (mPGES-1) and elevated levels of PGE2.

31 up-regulation of microsomal PGE synthase-1 (mPGES-1) and L-PGDS.

32 COX-2 and microsomal PGE synthase-1 (mPGES-1) and mPGES-2 are present in postsynaptic dendrit

33 fied microsomal prostaglandin E2 synthase-1 (mPGES-1) as a RET/PTC-inducible gene through subtraction

34 ed both COX-2 and microsomal PGE synthase-1 (mPGES-1) but not COX-1 in the Golgi apparatus.

35 ) and microsomal prostaglandin E synthase-1 (mPGES-1) by a yet unknown mechanism.

36 crosomal prostaglandin (PG) E(2) synthase-1 (mPGES-1) catalyzes isomerization of the cyclooxygenase p

37 Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of cyclooxygenase-deri

38 Microsomal prostaglandin E synthase-1 (mPGES-1) in myeloid and vascular cells differentially re

39 ssing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refra

40 Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that couples with cyclooxygenas

41 Microsomal prostaglandin E synthase-1 (mPGES-1) is a rate-limiting enzyme that is coupled with

42 Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of

43 Microsomal prostaglandin E (PGE) synthase-1 (mPGES-1) is an inducible enzyme that couples with cycloo

44 Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that specifically cataly

45 that microsomal prostaglandin E synthase-1 (mPGES-1) is induced in brain vascular cells that also ex

46 Microsomal prostaglandin E2 synthase-1 (mPGES-1) is known as an ideal target for next generation

47 osomal prostaglandin E2 (PGE(2)) synthase-1 (mPGES-1) was once proposed as a potentially promising ta

48 hibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 muM.

49 ced expression of microsomal PGE synthase-1 (mPGES-1), a key enzyme in PGE2 biosynthesis.

50 Microsomal prostaglandin E synthase-1 (mPGES-1), a membrane-associated protein, is critically i

51 Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostagla

52 inducible PGE2, microsomal PGE2 synthase-1 (mPGES-1), has emerged as an interesting drug target for

53 ugh inhibition of microsomal PGE synthase-1 (mPGES-1), not COX-2.

54 lism, microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase (PGDH), COX-2 and

55 osomal prostaglandin E(2) (PGE2) synthase-1 (mPGES-1), the enzyme generating PGE2, prevents blood-bra

56 ) and microsomal prostaglandin E synthase-1 (mPGES-1), which are involved in PGE2 production.

57 f COX enzymes and microsomal PGE synthase-1 (mPGES-1).

58 vels of COX-2 and microsomal PGE synthase-1 (mPGES-1).

59 Microsomal prostaglandin E2 synthase type 1 (mPGES-1) is responsible for the formation of the potent

60 Microsomal PGES-1(-/-) (mPGES-1(-/-)) mice were crossed into low-density lipopro

61 These findings have revealed a mPGES-1/prostaglandin E(2)/NO/cGMP pathway that appears

62 RET/PTC activated mPGES-1 gene transcription.

63 In addition, mPGES-1 null and heterozygous mice showed a marked reduc

64 n experiments using a siRNA directed against mPGES-1.

65 reatment, has recently been identified as an mPGES-1 inhibitor.

66 We show that BI1029539, an mPGES-1 inhibitor, prevented up-regulation of P-gp expre

67 remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progress

68 fold up-regulation of TLR4 expression via an mPGES-1-dependent pathway, whereas prolonged shear expos

69 Here we report that COX-1 and mPGES-1 mediate production of substantial amounts of PGE

70 ride, which elevated expression of COX-2 and mPGES-1 and produced PGE2, and this enhancement was inhi

71 IL-1RI positively correlated with COX-2 and mPGES-1 expression in both NM-C and NP-AERD fibroblasts.

72 e capacity of IL-1beta to increase COX-2 and mPGES-1 expression, which results in low PGE2 production

73 roteinase-2 protein and cyclooxygenase-2 and mPGES-1 mRNA expression.

74 IL-1beta increased mRNA levels for COX-2 and mPGES-1, but not for COX-1 or cPGES.

75 ed aortic expression of cyclooxygenase-2 and mPGES-1, increased aortic macrophage recruitment and vas

76 nthetic enzymes cyclooxygenase-2 (COX-2) and mPGES-1 are up-regulated in many cancers.

77 IL-1beta-induced IL-1RI, COX-2, and mPGES-1 expression levels were also lower in these cells

78 Alterations in IL-1RI, COX-2, and mPGES-1 expression that were found in NP-AERD fibroblast

79 cytosolic phospholipase A2alpha, COX-2, and mPGES-1 in the Golgi comprise a dedicated system for COX

80 ptor, cytosolic phospholipase A2, COX-2, and mPGES-1 increases P-gp protein expression and transport

81 in this pathway, cPLA2 type IVA, COX-2, and mPGES-1, were dramatically up-regulated at both the tran

82 Induction of COX2 and mPGES-1 expression by TLR2 stimulation or Mtb infection

83 expressed mRNAs of COX-1, COX-2, cPGES, and mPGES-1.

84 functional interaction between PPARgamma and mPGES-1 in controlling the process of pre-adipocyte diff

85 lation of adipogenesis between PPARgamma and mPGES-1.

86 cosanoid metabolism enzymes in wild type and mPGES-1-deficient macrophages.

87 ted insulin secretion equally in both WT and mPGES-1(-/-) islets, indicating that COX-2, not mPGES-1,

88 on was examined in isolated islets of WT and mPGES-1-deficient mice.

89 2, whereas there was no coexpression between mPGES-1 and cyclooxygenase-1.

90 ur findings depict a novel crosstalk between mPGES-1/PGE(2) and EGR1/beta-catenin signaling that is c

91 with in vivo rediversion of PG biosynthesis, mPGES-1-deleted vascular smooth muscle cells generated l

92 iated LPS-induced IL-33 generation from both mPGES-1-null and WT bmMFs, whereas EP1 and EP3 receptor

93 Male mice deficient in both mPGES-1 and LDLR (mPGES-1(-/-) LDLR(-/-)) and littermate

94 ffect on the attenuation of atherogenesis by mPGES-1 deletion in the low-density lipoprotein receptor

95 ane-1,20-dioic acid (PGE-M) was depressed by mPGES-1 deletion.

96 te that SphK1 regulates PGE(2) production by mPGES-1 expression via the p38 MAPK pathway, independent

97 ular smooth muscle cell and endothelial cell mPGES-1 deletion did not alter blood pressure at baselin

98 ular smooth muscle cell and endothelial cell mPGES-1-deficient mice exhibited a markedly exaggerated

99 In conclusion, myeloid cell mPGES-1 promotes atherogenesis in hyperlipidemic mice, c

100 In primary cultures of CD cells, mPGES-1 expression was significantly increased following

101 By contrast, mPGES-1 in vascular cells does not detectably influence

102 ared with the control (P<0.01); in contrast, mPGES-1 knockdown delayed tumor development and reduced

103 d terminal prostaglandin E synthases (cPGES, mPGES-1, and mPGES-2).

104 We aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs

105 tudy revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the ac

106 pro-inflammatory targets of curcumin (i.e., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-kapp

107 (VSMC-mPGES-1-KOs), or endothelial cells (EC-mPGES-1-KOs) were crossed into hyperlipidemic low-densit

108 ad implications for development of efficient mPGES-1 inhibitors, potential anti-inflammatory and anti

109 Compared with WT cells, bmMFs lacking either mPGES-1 or EP2 receptors displayed reduced LPS-induced I

110 In microsomal extracts, mPGES-1 protein was barely detectable in rat islets but

111 The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specif

112 Furthermore, 26 was selective for mPGES-1 inhibition versus other mechanisms in the prosta

113 654) demonstrated remarkable selectivity for mPGES-1 (IC(50) = 2.9 nM) over COX-1, COX-2, 5-LOX, and

114 itrite biosynthesis using cells derived from mPGES-1 wild-type (WT), heterozygous (Het), and null mic

115 Conditioned medium derived from mPGES-1-deficient macrophages less potently induced vasc

116 ramatic reduction in [3H]PGE2 formation from mPGES-1-/- macrophages compared with controls resulted i

117 lycollate-elicited macrophages isolated from mPGES-1-/- animals and genetically matched wild type con

118 ceptor knockout (LDLR(-/-)) mice to generate mPGES-1(-/-) LDLR(-/-)s.

119 High mPGES-1 expression also corresponded to poor survival of

120 ve determined the crystal structure of human mPGES-1 to 1.2 A resolution.

121 a high-resolution crystal structure of human mPGES-1 was presented, with Ser-127 being proposed as th

122 glutamate and in capillaries from humanized mPGES-1 mice after SE.

123 y isolating brain capillaries from humanized mPGES-1 mice to study P-gp levels.

124 ch mPGES-1 was silenced, thereby identifying mPGES-1 as a therapeutic target in the regulation of MMP

125 Importantly, mPGES-1 deletion also blocked the nuclear accumulation o

126 Most importantly, mPGES-1 deletion affected neither thrombogenesis nor blo

127 Here, we generated mice deficient in mPGES-1 in vascular smooth muscle cells, endothelial cel

128 Macrophage foam cells were depleted in mPGES-1(-/-) LDLR(-/-) lesions, whereas the total areas

129 lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type litterma

130 In contrast, we detected in mPGES-1-/- macrophages a >95% reduction in PGE2 producti

131 MCs expressing PGI synthase were enriched in mPGES-1(-/-) LDLR(-/-) lesions.

132 , but not 2,3-dinor-TxB(2), was increased in mPGES-1(-/-) LDLR(-/-)s.

133 ignificantly reduced 4 weeks after injury in mPGES-1 knockout mice compared with wild-type controls (

134 Interest in mPGES-1 inhibition can, in part, be attributed to the po

135 le breakdown product of nitric oxide (NO) in mPGES-1 WT MEFs compared with null MEFs.

136 ly increased in wild-type animals but not in mPGES-1 -/- mice.

137 e redirection of prostaglandin production in mPGES-1-/- cells provides novel insights into how a cell

138 um IgM and IgG were significantly reduced in mPGES-1 null mice.

139 [3H]hydroxyheptadecatrienoic acid release in mPGES-1-/- samples.

140 anti-inflammatory drugs based on studies in mPGES-1 knockouts.

141 wever, in neither case did IL-1beta increase mPGES-1 protein levels.

142 Moreover, TNF-alpha induced mPGES-1 by stimulating PC-PLC --> PKC --> NO --> cGMP --

143 , an activator of guanylate cyclase, induced mPGES-1.

144 sion in PCCL3 thyroid cells markedly induced mPGES-1 and COX-2.

145 Chronic salt loading remarkably induced mPGES-1 protein expression exclusively in the distal nep

146 athione-based analog, providing insight into mPGES-1 flexibility and potential for structure-based dr

147 This perspective introduces mPGES-1 as a key player within the network of eicosanoid

148 Mice lacking mPGES-1 (and therefore PGE2) developed arthritis normall

149 Mice lacking mPGES-1 (ptges(-/-) mice) and wild-type C57BL/6 controls

150 Mice lacking mPGES-1 conditionally in myeloid cells (Mac-mPGES-1-KOs)

151 Mice lacking mPGES-1 showed lower IL-33 levels and attenuated lung in

152 ale mice deficient in both mPGES-1 and LDLR (mPGES-1(-/-) LDLR(-/-)) and littermate LDLR(-/-) mice we

153 d pirinixic acids represent potent dual 5-LO/mPGES-1 inhibitors with an attractive pharmacological pr

154 ured pirinixic acid derivatives as dual 5-LO/mPGES-1 inhibitors with improved potency (exemplified by

155 mPGES-1 conditionally in myeloid cells (Mac-mPGES-1-KOs), vascular smooth muscle cells (VSMC-mPGES-1

156 vealed markedly reduced atherogenesis in Mac-mPGES-1-KOs, which was concomitant with a reduction in o

157 e to vascular injury, implicating macrophage mPGES-1 as a cardiovascular drug target.

158 erapeutic rationale for targeting macrophage mPGES-1 in inflammatory cardiovascular diseases.

159 nship and pharmacological potential of major mPGES-1 inhibitor classes in light of recent insights fr

160 Mechanistically, mPGES-1-induced HCC cell proliferation, invasion and mig

161 Compared with WT mice, mPGES-1 null mice exhibited a significant reduction of h

162 In a mouse tumor xenograft model, mPGES-1-overexpressed cells formed palpable tumors at ea

163 antibody that specifically recognizes mouse mPGES-1 and dual-labeling for cell-specific markers, we

164 We therefore suggest that the CD14/NFAT/mPGES-1 pathway represents a possible target for antiinf

165 ES-1(-/-) islets, indicating that COX-2, not mPGES-1, mediates IL-1beta-induced PGE(2) production and

166 Notably, mPGES-1 is an inducible enzyme responsible for overprodu

167 We found that NADPH oxidase 5 (NOX5), mPGES-1 and iNOS were significantly increased in BE muco

168 The absence of mPGES-1 reduced the size and number of preneoplastic abe

169 lonocytes, resulting in increased amounts of mPGES-1 mRNA and protein.

170 Increased amounts of mPGES-1 were detected in inflamed intestinal mucosa from

171 as applied to characterize this new class of mPGES-1 inhibitors.

172 report, we characterize the contribution of mPGES-1 to cellular PGH2 metabolism in murine macrophage

173 strate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced art

174 Deletion of mPGES-1 also depressed urinary PGE-M, whereas it augment

175 Deletion of mPGES-1 decreased both the incidence (87.5% versus 27.3%

176 We show that deletion of mPGES-1 depressed PGE(2) expression, augmented PGI(2) ex

177 able, however, mice with genetic deletion of mPGES-1 have been generated that have given insight into

178 for the first time that genetic deletion of mPGES-1 in Apc-mutant mice results in marked and persist

179 Deletion of mPGES-1 in mice attenuates neointimal hyperplasia after

180 Deletion of mPGES-1 in the vasculature and myeloid cells differentia

181 the response to vascular injury, deletion of mPGES-1 in VSMCs, ECs, or both had no detectable phenoty

182 Deletion of mPGES-1 modulates experimentally evoked pain and inflamm

183 monstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its

184 Deletion of mPGES-1 protects against abdominal aortic aneurysm forma

185 Deletion of mPGES-1 reduced plaque burden in fat-fed LDLR(-/-)s but

186 The results show that genetic deletion of mPGES-1 results in a dramatic decrease in PGE2 productio

187 Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced

188 edly suppressed by myeloid cell depletion of mPGES-1 with decreased hyperplasia, leukocyte infiltrati

189 To determine whether the effect of mPGES-1 and PGE2 was localized to hematopoietic or nonhe

190 din E2 accounts for the protective effect of mPGES-1 deletion in atherosclerosis, augmentation of PGI

191 We also examined the effect of mPGES-1 deletion on carcinogen-induced colon cancer.

192 ld facilitate investigation of the effect of mPGES-1 genetic deletion on prostanoid biosynthesis in f

193 The effects of mPGES-1 on human cholangiocarcinoma cells were determine

194 cular injury, reflecting distinct effects of mPGES-1-derived PGE2 in these cell types on discrete cel

195 re standing at the threshold of a new era of mPGES-1-targeting anti-inflammatory drugs.

196 emical analyses to examine the expression of mPGES-1 in formalin-fixed, paraffin-embedded human chola

197 g the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts.

198 esponse-1 (Egr-1), a transcription factor of mPGES-1.

199 The impact of mPGES-1 deletion on formation of angiotensin II-induced

200 To further assess the importance of mPGES-1 to IL-1beta regulation of an islet physiologic r

201 ility of COX-2 but preserved inducibility of mPGES-1 on gene expression level were confirmed in an in

202 te cyclase activity blocked the induction of mPGES-1 by TNF-alpha.

203 ling as being important for the induction of mPGES-1 by TNF-alpha.

204 Finally, the induction of mPGES-1 was regulated, in part, through a positive feedb

205 The ubiquitous induction of mPGES-1-dependent PGE2 may be crucial for innate immune

206 membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin.

207 Inhibition of mPGES-1 has been proposed as a therapeutic strategy for

208 ic potential for pharmacologic inhibition of mPGES-1 in inflammatory conditions.

209 otential efficacy of selective inhibition of mPGES-1 in preventing or retarding aneurysm formation wa

210 Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and t

211 Selective inhibition of mPGES-1 might be a promising step to avoid cyclooxygenas

212 Interestingly, selective inhibition of mPGES-1 was also associated with a decrease in LPS-induc

213 Selective inhibition of mPGES-1 with either siRNA or isoform-selective inhibitor

214 Specific inhibitors of mPGES-1 are not yet available, however, mice with geneti

215 Inhibitors of mPGES-1 may be less likely than those selective for cycl

216 se prostaglandins suggest that inhibitors of mPGES-1 may be less likely to cause cardiovascular adver

217 These results suggest that inhibitors of mPGES-1 may retain their antiinflammatory efficacy by de

218 migration and invasion, whereas knockdown of mPGES-1 inhibited these parameters, in vitro.

219 ; in contrast, RNA interference knockdown of mPGES-1 inhibited tumor growth parameters.

220 ma cells with overexpression or knockdown of mPGES-1.

221 Lack of mPGES-1 in bone marrow-derived leukocytes negatively reg

222 modified mice, the cellular localization of mPGES-1 in the mouse brain has not been thoroughly deter

223 Overexpression of mPGES-1 in human cholangiocarcinoma cells increased tumo

224 these results suggest that overexpression of mPGES-1 in IBD is the result of Egr-1-mediated activatio

225 Forced overexpression of mPGES-1 in two HCC cell lines (Hep3B and Huh7) increased

226 r consideration the therapeutic potential of mPGES-1 inhibitors as adjuvant therapy for percutaneous

227 pacity of PGE(2) as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggestin

228 f what is known about the functional role of mPGES-1 for these centrally evoked symptoms is based on

229 The role of mPGES-1 in abdominal aortic aneurysm is unknown.

230 In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recover

231 ession of various human cancers, the role of mPGES-1 in carcinogenesis has not been determined.

232 have given insight into the specific role of mPGES-1 in eicosanoid biosynthesis in vivo and in perito

233 dy provides novel evidence for a key role of mPGES-1 in HCC growth and progression.

234 hepatocellular carcinoma (HCC), the role of mPGES-1 in hepatocarcinogenesis is not well established.

235 We investigated the role of mPGES-1 in human cholangiocarcinoma growth.

236 The present study examined the role of mPGES-1 in regulation of sodium balance and blood pressu

237 his study, we further elucidated the role of mPGES-1 in the humoral immune response.

238 The role of mPGES-1 in the response to vascular injury is unknown.

239 the natriuretic and antihypertensive role of mPGES-1 that likely contributes to blood pressure homeos

240 The cell selective roles of mPGES-1 in atherogenesis are unknown.

241 Germinal center formation in the spleen of mPGES-1 null and WT mice were similar after immunization

242 Stimulation of mPGES-1(-/-) VSMC and macrophages with bacterial LPS inc

243 We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to unde

244 We have also determined the structure of mPGES-1 in complex with a glutathione-based analog, prov

245 ntation (BMT) from either COX-2-deficient or mPGES-1-deficient mice into WT mice or macrophage-specif

246 in brain endothelial cells, but not in other mPGES-1-positive cells, was coexpressed with cyclooxygen

247 mply a widespread synthesis of PGE2 or other mPGES-1-dependent products in the mouse brain that may b

248 Consistently, pharmacological mPGES-1 inhibition directed pre-adipocyte differentiatio

249 The most potent mPGES-1 inhibitor was lonazolac derivative 22 (IC(5)(0)

250 lapatinib has been identified as a promising mPGES-1 inhibitor which may have significant anti-inflam

251 ever, there has been no clinically promising mPGES-1 inhibitor identified through traditional drug di

252 2/Cox-2) and prostaglandin E synthase (Ptges/mPGES-1) was compromised in IRE1alpha-deficient myeloid

253 onists emerge as potential therapy to reduce mPGES-1 expression and PGE(2) levels in inflammatory and

254 median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevat

255 -RAS and MEK1, RET/PTC was found to regulate mPGES-1 through Shc-RAS-MEK-ERK.

256 Accordingly, restoring mPGES-1 expression in IRE1alpha(KO) cancer cells rescues

257 Increasing evidence reveals mPGES-1 inhibitors as a safe alternative to nonsteroidal

258 The first selective mPGES-1 inhibitors recently entered clinical trials.

259 e for the first time that a highly selective mPGES-1 inhibitor (UK4b) can completely block further gr

260 e for the first time that a highly selective mPGES-1 inhibitor can effectively relieve POP as well as

261 ssue from mice lacking PPARgamma also showed mPGES-1 up-regulation and increased PGE2 levels.

262 Specifically, mPGES-1-derived PGE(2) induces the formation of EGR1-bet

263 tumor necrosis factor (TNF)-alpha stimulated mPGES-1 transcription in human colonocytes, resulting in

264 Following immune stimulation, mPGES-1 in brain endothelial cells, but not in other mPG

265 cell-intrinsic IRE1alpha activation sustains mPGES-1 expression, enabling production of the immunosup

266 for use as an effective analgesic targeting mPGES-1.

267 Our data show the feasibility of targeting mPGES-1 for cancer chemoprevention with the potential fo

268 vious studies in mice suggest that targeting mPGES-1 may be less likely to cause hypertension or thro

269 We conclude that mPGES-1 and PGE2-dependent phenotypic changes of nonhema

270 We demonstrated that mPGES-1 deficiency in nonhematopoietic cells was the cri

271 the data have consistently demonstrated that mPGES-1 is a truly promising target for treatment of POP

272 In addition, we provide evidence that mPGES-1 deficiency sensitized the hypertensive effect of

273 However, we found that mPGES-1 deficiency was associated with a disorganized va

274 Our data support the hypothesis that mPGES-1 induction in response to an inflammatory stimulu

275 These findings indicated that mPGES-1-derived PGE(2) was not required for allergen sen

276 d burst of PGE(2) production indicating that mPGES-1 mediates LPS-induced PGE(2) production in BMDM.

277 ng for cell-specific markers, we report that mPGES-1 is constitutively expressed in the mouse brain,

278 In addition, we show that mPGES-1 gene deletion and subsequent decrease in PGE2 le

279 Furthermore, we show that mPGES-1 gene deletion results in diversion of prostanoid

280 We show that mPGES-1 is expressed in human, rat, and mouse brain capi

281 In summary, our data show that mPGES-1, but not mPGES-2 or c-PGES isomerase, mediates L

282 We showed that mPGES-1 null mice had a significantly reduced incidence

283 -induced P-gp up-regulation and suggest that mPGES-1 inhibitors could potentially prevent P-gp up-reg

284 with interleukin (IL)-1beta, suggesting that mPGES-1 is critically important for PGE2 production.

285 and limited structural information about the mPGES-1 inhibitor binding site.

286 talytic domain and within a subpocket of the mPGES-1 active site.

287 Binding of Egr-1 to the GC box region of the mPGES-1 promoter was enhanced by treatment with TNF-alph

288 -alpha localized to the GC box region of the mPGES-1 promoter.

289 locked TNF-alpha-mediated stimulation of the mPGES-1 promoter.

290 Thus, mPGES-1 and its product, PGE(2), protect the pulmonary v

291 Thus, mPGES-1, a key microcirculation protector, constrains MI

292 -1 exhibited efficient catalytic coupling to mPGES-1.

293 ght be at risk of a hypertensive response to mPGES-1 inhibitors.

294 ed protein levels of COX-2, but unexpectedly mPGES-1 protein levels were low and unaffected.

295 Vascular mPGES-1 was augmented during atherogenesis in LDLR(-/-)s

296 S-1-KOs), vascular smooth muscle cells (VSMC-mPGES-1-KOs), or endothelial cells (EC-mPGES-1-KOs) were

297 and increased tumor weight (P<.01), whereas mPGES-1 knockdown delayed tumor formation and reduced tu

298 s have ever been reported to explore whether mPGES-1 is also a potential target for POP treatment.

299 markedly attenuated in macrophages in which mPGES-1 was silenced, thereby identifying mPGES-1 as a t

300 In SCID mice with tumor xenografts, mPGES-1 overexpression accelerated tumor formation and i