|
|
Blood, 15 March 2004, Vol. 103, No. 6, pp. 2196-2204.
Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-06-1980.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice
Hisamichi Yuda,
Yukihiko Adachi,
Osamu Taguchi,
Esteban C. Gabazza,
Osamu Hataji,
Hajime Fujimoto,
Shigenori Tamaki,
Kimiaki Nishikubo,
Kenji Fukudome,
Corina N. D'Alessandro-Gabazza,
Junko Maruyama,
Masahiko Izumizaki,
Michiko Iwase,
Ikuo Homma,
Ryo Inoue,
Haruhiko Kamada,
Tatsuya Hayashi,
Michael Kasper,
Bart N. Lambrecht,
Peter J. Barnes, and
Koji Suzuki
From the Third Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan; Department of Molecular Pathobiology, Mie University School of Medicine, Tsu-city, Mie, Japan; Department of Physiology, Mie University School of Medicine, Tsu, Mie, Japan; Department of Immunology, Saga Medical School, Saga, Japan; Second Department of Physiology, Showa University School of Medicine, Tokyo, Japan; Institute of Anatomy, Technical University of Dresden, Dresden, Germany; Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; and the National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Asthma is one of the most common diseases and is characterized by airway obstruction, airway inflammation, and increased airway responsiveness. Glucocorticoids are very effective in treatment, but their long-term use is associated with several side effects, so that new anti-inflammatory drugs are in development. Activated protein C (APC) is a serine protease with potent anti-inflammatory effects. This study evaluated the effect of inhaled APC on airway inflammation and hyperresponsiveness in a murine asthma model. Asthma was induced in BALB/c mice by exposure to chicken egg ovalbumin (OVA), and the effect of inhaled APC was assessed by administering prior to OVA exposure. Inhalation of APC significantly inhibited the expression of T helper 2 (Th2) cytokines, immunoglobulin E (IgE), eosinophilic inflammation, and hyperresponsiveness. APC also significantly suppressed the expression of Th2 cytokines and IgE from lymphocytes isolated from OVA-sensitized/challenged animals. In addition, binding of signal transducer and activator of transcription 6 (STAT6) and nuclear factor  B (NF-B) oligonucleotides to lung nuclear proteins was significantly reduced in mice treated with inhaled APC. In brief, the exogenous supplementation of APC inhibits the immunologic and inflammatory responses induced by Th2 cytokines in a mouse model of asthma and may represent a novel anti-inflammatory treatment.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. O. Mosnier, B. V. Zlokovic, and J. H. Griffin
The cytoprotective protein C pathway
Blood,
April 15, 2007;
109(8):
3161 - 3172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nishimura, T. Myles, A. M. Piliposky, P. N. Kao, G. J. Berry, and L. L. K. Leung
Thrombin-activatable procarboxypeptidase B regulates activated complement C5a in vivo
Blood,
March 1, 2007;
109(5):
1992 - 1997.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Shinagawa, J. A. Martin, V. A. Ploplis, and F. J. Castellino
Coagulation Factor Xa Modulates Airway Remodeling in a Murine Model of Asthma
Am. J. Respir. Crit. Care Med.,
January 15, 2007;
175(2):
136 - 143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. K. Chu, J. Cheng, J. S. Foley, B. H. Mecham, C. A. Owen, K. J. Haley, T. J. Mariani, I. S. Kohane, D. J. Tschumperlin, and J. M. Drazen
Induction of the Plasminogen Activator System by Mechanical Stimulation of Human Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol.,
December 1, 2006;
35(6):
628 - 638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Feistritzer, B. A. Mosheimer, D. H. Sturn, M. Riewald, J. R. Patsch, and C. J. Wiedermann
Endothelial Protein C Receptor-Dependent Inhibition of Migration of Human Lymphocytes by Protein C Involves Epidermal Growth Factor Receptor
J. Immunol.,
January 15, 2006;
176(2):
1019 - 1025.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Weijer, C. W. Wieland, S. Florquin, and T. van der Poll
A thrombomodulin mutation that impairs activated protein C generation results in uncontrolled lung inflammation during murine tuberculosis
Blood,
October 15, 2005;
106(8):
2761 - 2768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Okunishi, M. Dohi, K. Nakagome, R. Tanaka, S. Mizuno, K. Matsumoto, J.-i. Miyazaki, T. Nakamura, and K. Yamamoto
A Novel Role of Hepatocyte Growth Factor as an Immune Regulator through Suppressing Dendritic Cell Function
J. Immunol.,
October 1, 2005;
175(7):
4745 - 4753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. van der Poll, M. Levi, J. A. Nick, and E. Abraham
Activated Protein C Inhibits Local Coagulation after Intrapulmonary Delivery of Endotoxin in Humans
Am. J. Respir. Crit. Care Med.,
May 15, 2005;
171(10):
1125 - 1128.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
