| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Dermatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan;
Department of Advanced Medicine and Development, Bio Medical Laboratories, Inc., Saitama, Japan;
Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan;
¶ Department of Comprehensive Pathology and Immunology, Tokyo Medical and Dental University, Tokyo, Japan; and
|| Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan
PGD2 plays roles in allergic inflammation via specific receptors, the PGD receptor designated DP and CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells). We generated mutant mice carrying a targeted disruption of the CRTH2 gene to investigate the functional roles of CRTH2 in cutaneous inflammatory responses. CRTH2-deficent mice were fertile and grew normally. Ear-swelling responses induced by hapten-specific IgE were less pronounced in mutant mice, giving 35–55% of the responses of normal mice. Similar results were seen in mice treated with a hemopoietic PGD synthase inhibitor, HQL-79, or a CRTH2 antagonist, ramatroban. The reduction in cutaneous responses was associated with decreased infiltration of lymphocytes, eosinophils, and basophils and decreased production of macrophage-derived chemokine and RANTES at inflammatory sites. In models of chronic contact hypersensitivity induced by repeated hapten application, CRTH2 deficiency resulted in a reduction by approximately half of skin responses and low levels (63% of control) of serum IgE production, although in vivo migration of Langerhans cells and dendritic cells to regional lymph nodes was not impaired in CRTH2-deficient mice. In contrast, delayed-type hypersensitivity to SRBC and irritation dermatitis in mutant mice were the same as in wild-type mice. These findings indicate that the PGD2-CRTH2 system plays a significant role in chronic allergic skin inflammation. CRTH2 may represent a novel therapeutic target for treatment of human allergic disorders, including atopic dermatitis.
This article has been cited by other articles:
|
|
 |
|
  L. Xue, A. Barrow, and R. Pettipher Novel Function of CRTH2 in Preventing Apoptosis of Human Th2 Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway J. Immunol., June 15, 2009; 182(12): 7580 - 7586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schroder, N. Merten, J. M. Mathiesen, L. Martini, A. Kruljac-Letunic, F. Krop, A. Blaukat, Y. Fang, E. Tran, T. Ulven, et al. The C-terminal Tail of CRTH2 Is a Key Molecular Determinant That Constrains G{alpha}i and Downstream Signaling Cascade Activation J. Biol. Chem., January 9, 2009; 284(2): 1324 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Boehme, E. P. Chen, K. Franz-Bacon, R. Sasik, L. J. Sprague, T. W. Ly, G. Hardiman, and K. B. Bacon Antagonism of CRTH2 ameliorates chronic epicutaneous sensitization-induced inflammation by multiple mechanisms Int. Immunol., January 1, 2009; 21(1): 1 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schuligoi, M. Sedej, M. Waldhoer, A. Vukoja, E. M. Sturm, I. T. Lippe, B. A. Peskar, and A. Heinemann Prostaglandin H2 induces the migration of human eosinophils through the chemoattractant receptor homologous molecule of Th2 cells, CRTH2 J. Leukoc. Biol., January 1, 2009; 85(1): 136 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. Lukacs, A. A. Berlin, K. Franz-Bacon, R. Sasik, L. J. Sprague, T. W. Ly, G. Hardiman, S. A. Boehme, and K. B. Bacon CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L767 - L779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tajima, T. Murata, K. Aritake, Y. Urade, H. Hirai, M. Nakamura, H. Ozaki, and M. Hori Lipopolysaccharide Induces Macrophage Migration via Prostaglandin D2 and Prostaglandin E2 J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 493 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nomiya, M. Okano, T. Fujiwara, M. Maeda, Y. Kimura, K. Kino, M. Yokoyama, H. Hirai, K. Nagata, T. Hara, et al. CRTH2 Plays an Essential Role in the Pathophysiology of Cry j 1-Induced Pollinosis in Mice J. Immunol., April 15, 2008; 180(8): 5680 - 5688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shiraishi, K. Asano, K. Niimi, K. Fukunaga, M. Wakaki, J. Kagyo, T. Takihara, S. Ueda, T. Nakajima, T. Oguma, et al. Cyclooxygenase-2/Prostaglandin D2/CRTH2 Pathway Mediates Double-Stranded RNA-Induced Enhancement of Allergic Airway Inflammation J. Immunol., January 1, 2008; 180(1): 541 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Taniguchi, I. Mohri, H. Okabe-Arahori, K. Aritake, K. Wada, T. Kanekiyo, S. Narumiya, M. Nakayama, K. Ozono, Y. Urade, et al. Prostaglandin D2 Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury J. Neurosci., April 18, 2007; 27(16): 4303 - 4312. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
