| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Divisions of
*
Rheumatology and
Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109; and
Division of Chemistry II, Karolinska Institutet, MBB, Stockholm, Sweden
The selective induction of PGE2 synthesis in
inflammation suggests that a PGE synthase may be linked to an inducible
pathway for PG synthesis. We examined the expression of the recently
cloned inducible microsomal PGE synthase (mPGES) in synoviocytes from
patients with rheumatoid arthritis, its modulation by cytokines and
dexamethasone, and its linkage to the inducible cyclooxygenase-2.
Northern blot analysis showed that IL-1
or TNF-
treatment induces
mPGES mRNA from very low levels at baseline to maximum levels at
24 h. IL-1-induced mPGES mRNA was inhibited by dexamethasone in
a dose-dependent fashion. Western blot analysis demonstrated that mPGES
protein was induced by IL-1, and maximum expression was sustained
for up to 72 h. There was a coordinated up-regulation of
cyclooxygenase-2 protein, although peak expression was earlier.
Differential Western blot analysis of the microsomal and the cytosolic
fractions revealed that the induced expression of mPGES protein was
limited to the microsomal fraction. The detected mPGES protein was
catalytically functional as indicated by a 3-fold increase of PGES
activity in synoviocytes following treatment with IL-1; this
increased synthase activity was limited to the microsomal fraction. In
summary, these data demonstrate an induction of mPGES in rheumatoid
synoviocytes by proinflammatory cytokines. This novel pathway may be a
target for therapeutic intervention for patients with
arthritis.
This article has been cited by other articles:
|
|
 |
|
  D. Xu, S. E. Rowland, P. Clark, A. Giroux, B. Cote, S. Guiral, M. Salem, Y. Ducharme, R. W. Friesen, N. Methot, et al. MF63 [2-(6-Chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile], a Selective Microsomal Prostaglandin E Synthase-1 Inhibitor, Relieves Pyresis and Pain in Preclinical Models of Inflammation J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 754 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jegerschold, S.-C. Pawelzik, P. Purhonen, P. Bhakat, K. R. Gheorghe, N. Gyobu, K. Mitsuoka, R. Morgenstern, P.-J. Jakobsson, and H. Hebert Structural basis for induced formation of the inflammatory mediator prostaglandin E2 PNAS, August 12, 2008; 105(32): 11110 - 11115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Kojima, M. Kapoor, L. Yang, E. L. Fleishaker, M. R. Ward, S. U. Monrad, P. C. Kottangada, C. Q. Pace, J. A. Clark, J. G. Woodward, et al. Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice J. Immunol., June 15, 2008; 180(12): 8361 - 8368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Valvason, E. Musacchio, A. Pozzuoli, R. Ramonda, R. Aldegheri, and L. Punzi Influence of glucosamine sulphate on oxidative stress in human osteoarthritic chondrocytes: effects on HO-1, p22Phox and iNOS expression Rheumatology, January 1, 2008; 47(1): 31 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Han, B. Chen, and T. J. Smith Jak2 Dampens the Induction by IL-1beta of Prostaglandin Endoperoxide H Synthase 2 Expression in Human Orbital Fibroblasts: Evidence for Divergent Influence on the Prostaglandin E2 Biosynthetic Pathway J. Immunol., November 15, 2007; 179(10): 7147 - 7156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Samuelsson, R. Morgenstern, and P.-J. Jakobsson Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target Pharmacol. Rev., September 1, 2007; 59(3): 207 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Timmers, G. Pasterkamp, and D. P.V. de Kleijn Microsomal Prostaglandin E2 Synthase: A Safer Target than Cyclooxygenases? Mol. Interv., August 1, 2007; 7(4): 195 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mosca, N. Polentarutti, G. Mangano, C. Apicella, A. Doni, F. Mancini, M. De Bortoli, I. Coletta, L. Polenzani, G. Santoni, et al. Regulation of the microsomal prostaglandin E synthase-1 in polarized mononuclear phagocytes and its constitutive expression in neutrophils J. Leukoc. Biol., August 1, 2007; 82(2): 320 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Horita, E. Kuroda, T. Hachisuga, M. Kashimura, and U. Yamashita Induction of prostaglandin E2 production by leukemia inhibitory factor promotes migration of first trimester extravillous trophoblast cell line, HTR-8/SVneo Hum. Reprod., July 1, 2007; 22(7): 1801 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kapoor, F. Kojima, M. Qian, L. Yang, and L. J. Crofford Microsomal Prostaglandin E Synthase-1 Deficiency Is Associated with Elevated Peroxisome Proliferator-activated Receptor {gamma}: REGULATION BY PROSTAGLANDIN E2 VIA THE PHOSPHATIDYLINOSITOL 3-KINASE AND AKT PATHWAY J. Biol. Chem., February 23, 2007; 282(8): 5356 - 5366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kapoor, F. Kojima, M. Qian, L. Yang, and L. J. Crofford Shunting of prostanoid biosynthesis in microsomal prostaglandin E synthase-1 null embryo fibroblasts: regulatory effects on inducible nitric oxide synthase expression and nitrite synthesis FASEB J, November 1, 2006; 20(13): 2387 - 2389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Hayakawa, Y Fujiwara, M Hamaguchi, T Sugawa, M Okuyama, E Sasaki, T Watanabe, K Tominaga, N Oshitani, K Higuchi, et al. Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis Gut, April 1, 2006; 55(4): 450 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Pascual, E. M. Carr, M. C. Seeds, M. Guo, R. A. Panettieri Jr., S. P. Peters, and R. B. Penn Regulatory features of interleukin-1beta-mediated prostaglandin E2 synthesis in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L501 - L508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Ackerman IV, J. M. Robinson, and D. A. Kniss Despite Transcriptional and Functional Coordination, Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Largely Reside in Distinct Lipid Microdomains in WISH Epithelial Cells J. Histochem. Cytochem., November 1, 2005; 53(11): 1391 - 1401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Masse, S. Guiral, L.-J. Fortin, E. Cauchon, D. Ethier, J. Guay, and C. Brideau An Automated Multistep High-Throughput Screening Assay for the Identification of Lead Inhibitors of the Inducible Enzyme mPGES-1 J Biomol Screen, September 1, 2005; 10(6): 599 - 605. [Abstract] [PDF]
|
|
|
|
|
|
K. M. A. O'Reilly, R. P. Phipps, T. H. Thatcher, B. A. Graf, J. Van Kirk, and P. J. Sime Crystalline and amorphous silica differentially regulate the cyclooxygenase-prostaglandin pathway in pulmonary fibroblasts: implications for pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1010 - L1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sapirstein, H. Saito, S. J. Texel, T. A. Samad, E. O'Leary, and J. V. Bonventre Cytosolic phospholipase A2{alpha} regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1774 - R1782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Trebino, J. D. Eskra, T. S. Wachtmann, J. R. Perez, T. J. Carty, and L. P. Audoly Redirection of Eicosanoid Metabolism in mPGES-1-deficient Macrophages J. Biol. Chem., April 29, 2005; 280(17): 16579 - 16585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, H. Hanawa, T. Yoshida, R. Elnaggar, M. Hayashi, R. Watanabe, K. Toba, K. Yoshida, H. Chang, Y. Okura, et al. Effect of Hydrodynamics-Based Gene Delivery of Plasmid DNA Encoding Interleukin-1 Receptor Antagonist-Ig for Treatment of Rat Autoimmune Myocarditis: Possible Mechanism for Lymphocytes and Noncardiac Cells Circulation, April 5, 2005; 111(13): 1593 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shinji, T. Tsukui, A. Tatsuguchi, K. Shinoki, M. Kusunoki, K. Suzuki, T. Hiratsuka, K. Wada, S. Futagami, K. Miyake, et al. Induced microsomal PGE synthase-1 is involved in cyclooxygenase-2-dependent PGE2 production in gastric fibroblasts Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G308 - G315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Blaine, A. M. Meyer, G. Hurteau, M. Wick, J. A. Hankin, R. C. Murphy, A. J. Dannenberg, M. W. Geraci, K. Subbaramaiah, and R. A. Nemenoff Targeted over-expression of mPGES-1 and elevated PGE2 production is not sufficient for lung tumorigenesis in mice Carcinogenesis, January 1, 2005; 26(1): 209 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kamei, K. Yamakawa, Y. Takegoshi, M. Mikami-Nakanishi, Y. Nakatani, S. Oh-ishi, H. Yasui, Y. Azuma, N. Hirasawa, K. Ohuchi, et al. Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1 J. Biol. Chem., August 6, 2004; 279(32): 33684 - 33695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Guay, K. Bateman, R. Gordon, J. Mancini, and D. Riendeau Carrageenan-induced Paw Edema in Rat Elicits a Predominant Prostaglandin E2 (PGE2) Response in the Central Nervous System Associated with the Induction of Microsomal PGE2 Synthase-1 J. Biol. Chem., June 4, 2004; 279(23): 24866 - 24872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Boulet, M. Ouellet, K. P. Bateman, D. Ethier, M. D. Percival, D. Riendeau, J. A. Mancini, and N. Methot Deletion of Microsomal Prostaglandin E2 (PGE2) Synthase-1 Reduces Inducible and Basal PGE2 Production and Alters the Gastric Prostanoid Profile J. Biol. Chem., May 28, 2004; 279(22): 23229 - 23237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cheng, H. Afif, J. Martel-Pelletier, J.-P. Pelletier, X. Li, K. Farrajota, M. Lavigne, and H. Fahmi Activation of Peroxisome Proliferator-activated Receptor {gamma} Inhibits Interleukin-1{beta}-induced Membrane-associated Prostaglandin E2 Synthase-1 Expression in Human Synovial Fibroblasts by Interfering with Egr-1 J. Biol. Chem., May 21, 2004; 279(21): 22057 - 22065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Subbaramaiah, K. Yoshimatsu, E. Scherl, K. M. Das, K. D. Glazier, D. Golijanin, R. A. Soslow, T. Tanabe, H. Naraba, and A. J. Dannenberg Microsomal Prostaglandin E Synthase-1 Is Overexpressed in Inflammatory Bowel Disease: EVIDENCE FOR INVOLVEMENT OF THE TRANSCRIPTION FACTOR Egr-1 J. Biol. Chem., March 26, 2004; 279(13): 12647 - 12658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T J Jang, S K Min, J D Bae, K H Jung, J I Lee, J R Kim, and W S Ahn Expression of cyclooxygenase 2, microsomal prostaglandin E synthase 1, and EP receptors is increased in rat oesophageal squamous cell dysplasia and Barrett's metaplasia induced by duodenal contents reflux Gut, January 1, 2004; 53(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Premyslova, W. Li, N. Alfaidy, A. D. Bocking, K. Campbell, W. Gibb, and J. R. G. Challis Differential Expression and Regulation of Microsomal Prostaglandin E2 Synthase in Human Fetal Membranes and Placenta with Infection and in Cultured Trophoblast Cells J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6040 - 6047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sun, R. Ma, X. Cui, B. Campos, R. Webster, D. Brockman, and L. Myatt Glucocorticoids Induce Cytosolic Phospholipase A2 and Prostaglandin H Synthase Type 2 But Not Microsomal Prostaglandin E Synthase (PGES) and Cytosolic PGES Expression in Cultured Primary Human Amnion Cells J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5564 - 5571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Murakami, K. Nakashima, D. Kamei, S. Masuda, Y. Ishikawa, T. Ishii, Y. Ohmiya, K. Watanabe, and I. Kudo Cellular Prostaglandin E2 Production by Membrane-bound Prostaglandin E Synthase-2 via Both Cyclooxygenases-1 and -2 J. Biol. Chem., September 26, 2003; 278(39): 37937 - 37947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G. Cohen, T. Almahmeed, B. Du, D. Golijanin, J. O. Boyle, R. A. Soslow, K. Subbaramaiah, and A. J. Dannenberg Microsomal Prostaglandin E Synthase-1 Is Overexpressed in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., August 1, 2003; 9(9): 3425 - 3430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Trebino, J. L. Stock, C. P. Gibbons, B. M. Naiman, T. S. Wachtmann, J. P. Umland, K. Pandher, J.-M. Lapointe, S. Saha, M. L. Roach, et al. Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase PNAS, July 22, 2003; 100(15): 9044 - 9049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Thoren, R. Weinander, S. Saha, C. Jegerschold, P. L. Pettersson, B. Samuelsson, H. Hebert, M. Hamberg, R. Morgenstern, and P.-J. Jakobsson Human Microsomal Prostaglandin E Synthase-1: PURIFICATION, FUNCTIONAL CHARACTERIZATION, AND PROJECTION STRUCTURE DETERMINATION J. Biol. Chem., June 13, 2003; 278(25): 22199 - 22209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kamei, M. Murakami, Y. Nakatani, Y. Ishikawa, T. Ishii, and I. Kudo Potential Role of Microsomal Prostaglandin E Synthase-1 in Tumorigenesis J. Biol. Chem., May 23, 2003; 278(21): 19396 - 19405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Parapuram, R. Ganti, R. C. Hunt, and D. M. Hunt Vitreous Induces Components of the Prostaglandin E2 Pathway in Human Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1767 - 1774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Meadows, A. L. W. Eis, D. E. Brockman, and L. Myatt Expression and Localization of Prostaglandin E Synthase Isoforms in Human Fetal Membranes in Term and Preterm Labor J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 433 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Ivanov, R. S. Pero, A. C. Scheck, and A. A. Romanovsky Prostaglandin E2-synthesizing enzymes in fever: differential transcriptional regulation Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2002; 283(5): R1104 - R1117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Han and T. J. Smith Cytoplasmic Prostaglandin E2 Synthase Is Dominantly Expressed in Cultured KAT-50 Thyrocytes, Cells That Express Constitutive Prostaglandin-endoperoxide H Synthase-2. BASIS FOR LOW PROSTAGLANDIN E2 PRODUCTION J. Biol. Chem., September 20, 2002; 277(39): 36897 - 36903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Naraba, C. Yokoyama, N. Tago, M. Murakami, I. Kudo, M. Fueki, S. Oh-ishi, and T. Tanabe Transcriptional Regulation of the Membrane-associated Prostaglandin E2 Synthase Gene. ESSENTIAL ROLE OF THE TRANSCRIPTION FACTOR Egr-1 J. Biol. Chem., August 2, 2002; 277(32): 28601 - 28608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lazarus, C. J. Munday, N. Eguchi, S. Matsumoto, G. J. Killian, B. K. Kubata, and Y. Urade Immunohistochemical Localization of Microsomal PGE Synthase-1 and Cyclooxygenases in Male Mouse Reproductive Organs Endocrinology, June 1, 2002; 143(6): 2410 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. McEvoy, E. A. Murphy, T. Ponnio, O. M. Conneely, B. Bresnihan, O. FitzGerald, and E. P. Murphy Activation of Nuclear Orphan Receptor NURR1 Transcription by NF-{kappa}B and Cyclic Adenosine 5'-Monophosphate Response Element-Binding Protein in Rheumatoid Arthritis Synovial Tissue J. Immunol., March 15, 2002; 168(6): 2979 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yoshimatsu, D. Golijanin, P. B. Paty, R. A. Soslow, P.-J. Jakobsson, R. A. DeLellis, K. Subbaramaiah, and A. J. Dannenberg Inducible Microsomal Prostaglandin E Synthase Is Overexpressed in Colorectal Adenomas and Cancer Clin. Cancer Res., December 1, 2001; 7(12): 3971 - 3976. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
