The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Uehara, A.
Right arrow Articles by Takada, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Uehara, A.
Right arrow Articles by Takada, H.
The Journal of Immunology, 2002, 169: 4594-4603.
Copyright © 2002 by The American Association of Immunologists

Activation of Human Oral Epithelial Cells by Neutrophil Proteinase 3 Through Protease-Activated Receptor-21

Akiko Uehara*, Shunji Sugawara2,*, Koji Muramoto{dagger} and Haruhiko Takada*

* Department of Microbiology and Immunology, School of Dentistry, and {dagger} Laboratory of Biomolecular Function, Graduate School of Life Sciences, Tohoku University, Sendai, Japan

Proteinase 3 (PR3), a 29-kDa serine proteinase secreted from activated neutrophils, also exists in a membrane-bound form, and is suggested to actively contribute to inflammatory processes. The present study focused on the mechanism by which PR3 activates human oral epithelial cells. PR3 activated the epithelial cells in culture to produce IL-8 and monocyte chemoattractant protein-1 and to express ICAM-1 in a dose- and time-dependent manner. Incubation of the epithelial cells for 24 h with PR3 resulted in a significant increase in the adhesion to neutrophils, which was reduced to baseline levels in the presence of anti-ICAM-1 mAb. Activation of the epithelial cells by PR3 was inhibited by serine proteinase inhibitors and serum. The epithelial cells strongly express protease-activated receptor (PAR)-1 and PAR-2 mRNA and weakly express PAR-3 mRNA. The expression of PAR-2 on the cell surface was promoted by PR3, and inhibited by cytochalasin B, but not by cycloheximide. PR3 cleaved the peptide corresponding to the N terminus of PAR-2 with exposure of its tethered ligand. Treatment with trypsin, an agonist for PAR-2, and a synthetic PAR-2 agonist peptide induced intracellular Ca2+ mobilization, and rendered cells refractory to subsequent stimulation with PR3 and vice versa. The production of cytokine induced by PR3 and the PAR-2 agonist peptide was completely abolished by a phospholipase C inhibitor. These findings suggest that neutrophil PR3 activates oral epithelial cells through G protein-coupled PAR-2 and actively participates in the process of inflammation such as periodontitis.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. C. Chin, W. Y. Lee, A. Nusrat, N. Vergnolle, and C. A. Parkos
Neutrophil-mediated Activation of Epithelial Protease-Activated Receptors-1 and -2 Regulates Barrier Function and Transepithelial Migration
J. Immunol., October 15, 2008; 181(8): 5702 - 5710.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
A. Uehara, M. Naito, T. Imamura, J. Potempa, J. Travis, K. Nakayama, and H. Takada
Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis
J. Med. Microbiol., April 1, 2008; 57(4): 500 - 507.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Akk, P. M. Simmons, H. W. Chan, E. Agapov, M. J. Holtzman, M. H. Grayson, and C. T. N. Pham
Dipeptidyl Peptidase I-Dependent Neutrophil Recruitment Modulates the Inflammatory Response to Sendai Virus Infection
J. Immunol., March 1, 2008; 180(5): 3535 - 3542.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
H. Dommisch, W. O. Chung, M. G. Rohani, D. Williams, M. Rangarajan, M. A. Curtis, and B. A. Dale
Protease-Activated Receptor 2 Mediates Human Beta-Defensin 2 and CC Chemokine Ligand 20 mRNA Expression in Response to Proteases Secreted by Porphyromonas gingivalis
Infect. Immun., September 1, 2007; 75(9): 4326 - 4333.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
T. Nishioka, T. Kuroishi, Y. Sugawara, Z. Yu, T. Sasano, Y. Endo, and S. Sugawara
Induction of serum IL-18 with Propionibacterium acnes and lipopolysaccharide in phagocytic macrophage-inactivated mice
J. Leukoc. Biol., August 1, 2007; 82(2): 327 - 334.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
L. Yin and B. A. Dale
Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human {beta}-defensin-2
J. Med. Microbiol., July 1, 2007; 56(7): 976 - 987.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. Csernok, M. Ai, W. L. Gross, D. Wicklein, A. Petersen, B. Lindner, P. Lamprecht, J. U. Holle, and B. Hellmich
Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway
Blood, June 1, 2006; 107(11): 4440 - 4448.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. Camerer, I. Cornelissen, H. Kataoka, D. N. Duong, Y.-W. Zheng, and S. R. Coughlin
Roles of protease-activated receptors in a mouse model of endotoxemia
Blood, May 15, 2006; 107(10): 3912 - 3921.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. Chignard and D. Pidard
Neutrophil and Pathogen Proteinases versus Proteinase-Activated Receptor-2 Lung Epithelial Cells: More Terminators than Activators.
Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 394 - 398.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
Y. Hirota, Y. Osuga, T. Hirata, M. Harada, C. Morimoto, O. Yoshino, K. Koga, T. Yano, O. Tsutsumi, and Y. Taketani
Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells
Hum. Reprod., December 1, 2005; 20(12): 3547 - 3553.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
K. Ikawa, T. Nishioka, Z. Yu, Y. Sugawara, J. Kawagoe, T. Takizawa, V. Primo, B. Nikolic, T. Kuroishi, T. Sasano, et al.
Involvement of neutrophil recruitment and protease-activated receptor 2 activation in the induction of IL-18 in mice
J. Leukoc. Biol., November 1, 2005; 78(5): 1118 - 1126.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Uehara, K. Muramoto, T. Imamura, K. Nakayama, J. Potempa, J. Travis, S. Sugawara, and H. Takada
Arginine-Specific Gingipains from Porphyromonas gingivalis Stimulate Production of Hepatocyte Growth Factor (Scatter Factor) through Protease-Activated Receptors in Human Gingival Fibroblasts in Culture
J. Immunol., November 1, 2005; 175(9): 6076 - 6084.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
Y. Hirota, Y. Osuga, T. Hirata, K. Koga, O. Yoshino, M. Harada, C. Morimoto, E. Nose, T. Yano, O. Tsutsumi, et al.
Evidence for the Presence of Protease-Activated Receptor 2 and Its Possible Implication in Remodeling of Human Endometrium
J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1662 - 1669.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
A. Uehara, Y. Sugawara, T. Sasano, H. Takada, and S. Sugawara
Proinflammatory Cytokines Induce Proteinase 3 as Membrane-Bound and Secretory Forms in Human Oral Epithelial Cells and Antibodies to Proteinase 3 Activate the Cells through Protease-Activated Receptor-2
J. Immunol., September 15, 2004; 173(6): 4179 - 4189.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
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]

Home page
 Crit. Rev. Oral Biol. Med.Home page
F.T. Lundy and G.J. Linden
NEUROPEPTIDES AND NEUROGENIC MECHANISMS IN ORAL AND PERIODONTAL INFLAMMATION
Crit. Rev. Oral. Biol. Med., March 1, 2004; 15(2): 82 - 98.
[Abstract] [Full Text]

Home page
 Infect. Immun.Home page
A. Takayama, A. Satoh, T. Ngai, T. Nishimura, K. Ikawa, T. Matsuyama, H. Shimauchi, H. Takada, and S. Sugawara
Augmentation of Actinobacillus actinomycetemcomitans Invasion of Human Oral Epithelial Cells and Up-Regulation of Interleukin-8 Production by Saliva CD14
Infect. Immun., October 1, 2003; 71(10): 5598 - 5604.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 Innate ImmunityHome page
S. Sugawara, A. Uehara, R. Tamai, and H. Takada
Innate immune responses in oral mucosa
Innate Immunity, December 1, 2002; 8(6): 465 - 468.
[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.