| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, January 22, 1996, and in revised form, April 1, 1996)
From the The proteinase-activated receptor 2 (PAR-2)
belongs to the family of seven transmembrane region receptors, and,
like the related thrombin receptor, it is activated by specific
proteolytic cleavage of its extracellular amino terminus. It is not
known which proteinase is the physiological activator of the PAR-2, but
candidates can be found among the enzymes involved in the inflammatory
cascade systems. Here, we have studied the effects of various mediators
on the expression of the PAR-2 and the thrombin receptor in cultured
human umbilical vein endothelial cells. Stimulation with the cytokines
tumor necrosis factor
Volume 271, Number 25,
Issue of June 21, 1996
pp. 14910-14915
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
COMPARISON WITH THE THROMBIN RECEPTOR
,
Division of Molecular Neurobiology, The
Wallenberg Laboratory, Lund University, Sweden and ¶ COR
Therapeutics Inc., San Francisco, California 94080
or interleukin-1 as well as bacterial
lipopolysaccharide elevated the expression of PAR-2 in a
dose-dependent manner. The time course of induction after
cytokine stimulation was similar to those published for the adhesion
molecules intercellular adhesion molecule-1 and vascular cell adhesion
molecule-1. After 20 h of stimulation, PAR-2 mRNA and protein
levels were increased to 5-10-fold basal values, and, in the continued
presence of tumor necrosis factor , PAR-2 mRNA expression was
found to remain elevated for up to 4 days. In contrast, the thrombin
receptor gene was not induced by any of these inflammatory mediators.
The responses to phorbol ester treatment also differed between the two
genes. Thrombin receptor mRNA levels decreased steadily up to
20 h, whereas PAR-2 mRNA levels first rose to about 3-fold
basal values at 4 h before decreasing again. Cell surface protein
levels of both receptors were decreased after 20 h of phorbol
ester stimulation. Elevating intracellular cAMP levels by treatment
with forskolin resulted in decreased expression of both receptors, and
inhibition of cAMP degradation appeared to blunt the cytokine-induced
increase in PAR-2 expression. The induction of the PAR-2 by cytokine
treatment supports the concept of PAR-2 involvement in the acute
inflammatory response.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Feld, V. M. Shpacovitch, C. Ehrhardt, C. Kerkhoff, M. D. Hollenberg, N. Vergnolle, S. Ludwig, and M. Steinhoff Agonists of Proteinase-Activated Receptor-2 Enhance IFN-{gamma}-Inducible Effects on Human Monocytes: Role in Influenza A Infection J. Immunol., May 15, 2008; 180(10): 6903 - 6910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F. M. Wouters, K. H. Groenewegen, M. A. Dentener, and J. H. J. Vernooy Systemic Inflammation in Chronic Obstructive Pulmonary Disease: The Role of Exacerbations Proceedings of the ATS, December 1, 2007; 4(8): 626 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ostrowska, E. Sokolova, and G. Reiser PAR-2 activation and LPS synergistically enhance inflammatory signaling in airway epithelial cells by raising PAR expression level and interleukin-8 release Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1208 - L1218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Vesey, W. A. Kruger, P. Poronnik, G. C. Gobe, and D. W. Johnson Proinflammatory and proliferative responses of human proximal tubule cells to PAR-2 activation Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1441 - F1449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Jiang, A. Zatta, H. Kin, N. Wang, J. G. Reeves, J. Mykytenko, J. Deneve, Z.-Q. Zhao, R. A. Guyton, and J. Vinten-Johansen PAR-2 activation at the time of reperfusion salvages myocardium via an ERK1/2 pathway in in vivo rat hearts Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2845 - H2852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Moussa, J. Apostolopoulos, P. Davenport, J. Tchongue, and P. G. Tipping Protease-Activated Receptor-2 Augments Experimental Crescentic Glomerulonephritis Am. J. Pathol., September 1, 2007; 171(3): 800 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Seitz, S. Hess, H. Schulz, R. Eckl, G. Busch, H. P. Montens, R. Brandl, S. Seidl, A. Schomig, and I. Ott Membrane-Type Serine Protease-1/Matriptase Induces Interleukin-6 and -8 in Endothelial Cells by Activation of Protease-Activated Receptor-2: Potential Implications in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 769 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ramachandran, L. R. Sadofsky, Y. Xiao, A. Botham, M. Cowen, A. H. Morice, and S. J Compton Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4 Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L788 - L798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kida, H. Inoue, T. Shimizu, and K. Kuwano Serratia marcescens Serralysin Induces Inflammatory Responses through Protease-Activated Receptor 2 Infect. Immun., January 1, 2007; 75(1): 164 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hirano The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 27 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ruf Flow perturbation is linked to endothelial par signaling. Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 962 - 964. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Syeda, J. Grosjean, R. A. Houliston, R. J. Keogh, T. D. Carter, E. Paleolog, and C. P. D. Wheeler-Jones Cyclooxygenase-2 Induction and Prostacyclin Release by Protease-activated Receptors in Endothelial Cells Require Cooperation between Mitogen-activated Protein Kinase and NF-{kappa}B Pathways J. Biol. Chem., April 28, 2006; 281(17): 11792 - 11804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Holzhausen, L. C. Spolidorio, R. P. Ellen, M.-C. Jobin, M. Steinhoff, P. Andrade-Gordon, and N. Vergnolle Protease-Activated Receptor-2 Activation: A Major Role in the Pathogenesis of Porphyromonas gingivalis Infection Am. J. Pathol., April 1, 2006; 168(4): 1189 - 1199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Cleator, W. Q. Zhu, D. E. Vaughan, and H. E. Hamm Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP Blood, April 1, 2006; 107(7): 2736 - 2744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Lidington, R. Steinberg, A. R. Kinderlerer, R. C. Landis, M. Ohba, A. Samarel, D. O. Haskard, and J. C. Mason A role for proteinase-activated receptor 2 and PKC-{epsilon} in thrombin-mediated induction of decay-accelerating factor on human endothelial cells Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1437 - C1447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Roviezzo, M. Bucci, V. Brancaleone, A. Di Lorenzo, P. Geppetti, S. Farneti, L. Parente, G. Lungarella, S. Fiorucci, and G. Cirino Proteinase-Activated Receptor-2 Mediates Arterial Vasodilation in Diabetes Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2349 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Johansson, C. Lawson, M. Dabare, D. Syndercombe-Court, A. C. Newland, G. L. Howells, and M. G. Macey Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1{beta} J. Leukoc. Biol., October 1, 2005; 78(4): 967 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Noorbakhsh, N. Vergnolle, J. C. McArthur, C. Silva, M. Vodjgani, P. Andrade-Gordon, M. D. Hollenberg, and C. Power Proteinase-Activated Receptor-2 Induction by Neuroinflammation Prevents Neuronal Death during HIV Infection J. Immunol., June 1, 2005; 174(11): 7320 - 7329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Riewald and W. Ruf Protease-activated Receptor-1 Signaling by Activated Protein C in Cytokine-perturbed Endothelial Cells Is Distinct from Thrombin Signaling J. Biol. Chem., May 20, 2005; 280(20): 19808 - 19814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ahamed, M. Belting, and W. Ruf Regulation of tissue factor-induced signaling by endogenous and recombinant tissue factor pathway inhibitor 1 Blood, March 15, 2005; 105(6): 2384 - 2391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann, N. Vergnolle, T. A. Luger, and M. D. Hollenberg Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response Endocr. Rev., February 1, 2005; 26(1): 1 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Masamune, K. Kikuta, M. Satoh, N. Suzuki, and T. Shimosegawa Protease-Activated Receptor-2-Mediated Proliferation and Collagen Production of Rat Pancreatic Stellate Cells J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 651 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Busch, I. Seitz, B. Steppich, S. Hess, R. Eckl, A. Schomig, and I. Ott Coagulation Factor Xa Stimulates Interleukin-8 Release in Endothelial Cells and Mononuclear Leukocytes: Implications in Acute Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 461 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. O. Chung, S. R. Hansen, D. Rao, and B. A. Dale Protease-Activated Receptor Signaling Increases Epithelial Antimicrobial Peptide Expression J. Immunol., October 15, 2004; 173(8): 5165 - 5170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ahamed and W. Ruf Protease-activated Receptor 2-dependent Phosphorylation of the Tissue Factor Cytoplasmic Domain J. Biol. Chem., May 28, 2004; 279(22): 23038 - 23044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Napoli, F de Nigris, J L Wallace, M D Hollenberg, G Tajana, G De Rosa, V Sica, and G Cirino Evidence that protease activated receptor 2 expression is enhanced in human coronary atherosclerotic lesions J. Clin. Pathol., May 1, 2004; 57(5): 513 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shimizu, J. Nishihira, H. Watanabe, R. Abe, A. Honda, T. Ishibashi, and H. Shimizu Macrophage Migration Inhibitory Factor Is Induced by Thrombin and Factor Xa in Endothelial Cells J. Biol. Chem., April 2, 2004; 279(14): 13729 - 13737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. OSSOVSKAYA and N. W. BUNNETT Protease-Activated Receptors: Contribution to Physiology and Disease Physiol Rev, April 1, 2004; 84(2): 579 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yamamoto-Tabata, S. McDonagh, H.-T. Chang, S. Fisher, and L. Pereira Human Cytomegalovirus Interleukin-10 Downregulates Metalloproteinase Activity and Impairs Endothelial Cell Migration and Placental Cytotrophoblast Invasiveness In Vitro J. Virol., March 15, 2004; 78(6): 2831 - 2840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pawlinski, B. Pedersen, G. Schabbauer, M. Tencati, T. Holscher, W. Boisvert, P. Andrade-Gordon, R. D. Frank, and N. Mackman Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia Blood, February 15, 2004; 103(4): 1342 - 1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Lan, G. A. Stewart, R. G. Goldie, and P. J. Henry Altered expression and in vivo lung function of protease-activated receptors during influenza A virus infection in mice Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L388 - L398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Weidinger, A. Mayerhofer, M.B. Frungieri, V. Meineke, J. Ring, and F.M. Kohn Mast cell-sperm interaction: evidence for tryptase and proteinase-activated receptors in the regulation of sperm motility Hum. Reprod., December 1, 2003; 18(12): 2519 - 2524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. SEELIGER, C. K. DERIAN, N. VERGNOLLE, N. W. BUNNETT, R. NAWROTH, M. SCHMELZ, P.-Y. VON DER WEID, J. BUDDENKOTTE, C. SUNDERKOTTER, D. METZE, et al. Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo FASEB J, October 1, 2003; 17(13): 1871 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Colognato, J. R. Slupsky, M. Jendrach, L. Burysek, T. Syrovets, and T. Simmet Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells Blood, October 1, 2003; 102(7): 2645 - 2652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Cederqvist, C. Haglund, P. Heikkila, T. Sorsa, T. Tervahartiala, U.-H. Stenman, and S. Andersson Pulmonary Trypsin-2 in the Development of Bronchopulmonary Dysplasia in Preterm Infants Pediatrics, September 1, 2003; 112(3): 570 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fiorucci, E. Distrutti, B. Federici, B. Palazzetti, M. Baldoni, A. Morelli, and G. Cirino PAR-2 modulates pepsinogen secretion from gastric-isolated chief cells Am J Physiol Gastrointest Liver Physiol, August 8, 2003; 285(3): G611 - G620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Grandaliano, P. Pontrelli, G. Cerullo, R. Monno, E. Ranieri, M. Ursi, A. Loverre, L. Gesualdo, and F. P. Schena Protease-Activated Receptor-2 Expression in IgA Nephropathy: A Potential Role in the Pathogenesis of Interstitial Fibrosis J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2072 - 2083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Major, R. J. Santulli, C. K. Derian, and P. Andrade-Gordon Extracellular Mediators in Atherosclerosis and Thrombosis: Lessons From Thrombin Receptor Knockout Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 931 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Uehara, K. Muramoto, H. Takada, and S. Sugawara Neutrophil Serine Proteinases Activate Human Nonepithelial Cells to Produce Inflammatory Cytokines Through Protease-Activated Receptor 2 J. Immunol., June 1, 2003; 170(11): 5690 - 5696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Robin, R. Kharbanda, P. Mclean, R. Campbell, and P. Vallance Protease-Activated Receptor 2-Mediated Vasodilatation in Humans In Vivo: Role of Nitric Oxide and Prostanoids Circulation, February 25, 2003; 107(7): 954 - 959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lang, P. I. Song, F. J. Legat, R. M. Lavker, B. Harten, H. Kalden, E. F. Grady, N. W. Bunnett, C. A. Armstrong, and J. C. Ansel Human Corneal Epithelial Cells Express Functional PAR-1 and PAR-2 Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 99 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Landis Aprotinin: Antithrombotic and Vasoactive Mechanisms of Action Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2002; 6(4): 307 - 312. [Abstract] [PDF]
|
|
|
|
|
|
F. Schmidlin, S. Amadesi, K. Dabbagh, D. E. Lewis, P. Knott, N. W. Bunnett, P. R. Gater, P. Geppetti, C. Bertrand, and M. E. Stevens Protease-Activated Receptor 2 Mediates Eosinophil Infiltration and Hyperreactivity in Allergic Inflammation of the Airway J. Immunol., November 1, 2002; 169(9): 5315 - 5321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Uehara, S. Sugawara, K. Muramoto, and H. Takada Activation of Human Oral Epithelial Cells by Neutrophil Proteinase 3 Through Protease-Activated Receptor-2 J. Immunol., October 15, 2002; 169(8): 4594 - 4603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Milia, M. B. Salis, T. Stacca, A. Pinna, P. Madeddu, M. Trevisani, P. Geppetti, and C. Emanueli Protease-Activated Receptor-2 Stimulates Angiogenesis and Accelerates Hemodynamic Recovery in a Mouse Model of Hindlimb Ischemia Circ. Res., August 23, 2002; 91(4): 346 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Napoli, F. De Nigris, C. Cicala, J. L. Wallace, G. Caliendo, M. Condorelli, V. Santagada, and G. Cirino Protease-activated receptor-2 activation improves efficiency of experimental ischemic preconditioning Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2004 - H2010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Camerer, H. Kataoka, M. Kahn, K. Lease, and S. R. Coughlin Genetic Evidence That Protease-activated Receptors Mediate Factor Xa Signaling in Endothelial Cells J. Biol. Chem., May 3, 2002; 277(18): 16081 - 16087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Maree and D. Fitzgerald PAR2 Is Partout and Now in the Heart Circ. Res., March 8, 2002; 90(4): 366 - 368. [Full Text] [PDF]
|
|
|
|
|
|
P. G. McLean, D. Aston, D. Sarkar, and A. Ahluwalia Protease-Activated Receptor-2 Activation Causes EDHF-Like Coronary Vasodilation: Selective Preservation in Ischemia/Reperfusion Injury: Involvement of Lipoxygenase Products, VR1 Receptors, and C-Fibers Circ. Res., March 8, 2002; 90(4): 465 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mall, T. Gonska, J. Thomas, S. Hirtz, R. Schreiber, and K. Kunzelmann Activation of ion secretion via proteinase-activated receptor-2 in human colon Am J Physiol Gastrointest Liver Physiol, February 1, 2002; 282(2): G200 - G210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Miotto, M D Hollenberg, N W Bunnett, A Papi, F Braccioni, P Boschetto, F Rea, A Zuin, P Geppetti, M Saetta, et al. Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers Thorax, February 1, 2002; 57(2): 146 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kunzelmann and M. Mall Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease Physiol Rev, January 1, 2002; 82(1): 245 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fiorucci, A. Mencarelli, B. Palazzetti, E. Distrutti, N. Vergnolle, M. D. Hollenberg, J. L. Wallace, A. Morelli, and G. Cirino Proteinase-activated receptor 2 is an anti-inflammatory signal for colonic lamina propria lymphocytes in a mouse model of colitis PNAS, November 20, 2001; 98(24): 13936 - 13941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Hoogerwerf, L. Zou, M. Shenoy, D. Sun, M. A. Micci, H. Lee-Hellmich, S. Y. Xiao, J. H. Winston, and P. J. Pasricha The Proteinase-Activated Receptor 2 Is Involved in Nociception J. Neurosci., November 15, 2001; 21(22): 9036 - 9042. [Abstract] [Full Text] [PDF]
|
|
|
|
