| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Medicine and
Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada;
University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
§
Department of Pediatrics, Chonbuk National University, Chonju, Chonbuk, Korea; and
¶
Institute for Medical Sciences, Dongsan Medical Centre, Taegu, Korea
Syk protein tyrosine kinase (PTK) is involved in signaling in
leukocytes. In macrophages, Fc
-receptor cross-linking induces Syk
PTK phosphorylation and activation, resulting in Syk-dependent events
required for phagocytosis and mediator release. We hypothesized that
Syk antisense oligodeoxynucleotides (ASO) delivered by aerosol to rat
lungs in vivo would depress Syk PTK expression, mediator release from
alveolar macrophages, and Syk-dependent pulmonary inflammation. RT-PCR
and RT-in situ PCR demonstrated that aerosolized Syk ASO administration
reduced Syk mRNA expression from alveolar macrophages compared with
cells isolated from sham-treated rats. Western blot analysis confirmed
that Syk PTK expression was reduced after Syk ASO treatment. Compared
with sham-treated rats (scrambled oligodeoxynucleotide), Syk ASO
treatment suppressed Fc-receptor-mediated nitric oxide (86.0 ±
8.3%) and TNF (73.1 ± 3.1%) production by alveolar macrophages
stimulated with IgG-anti-IgG complexes. In contrast,
Fc-receptor-induced IL-1ß release was unaffected by Syk ASO
treatment. Additionally, Syk ASO suppressed Ag-induced pulmonary
inflammation, suggesting that Syk ASO may prove useful as an
anti-inflammatory therapy in disorders such as
asthma.
This article has been cited by other articles:
|
|
 |
|
  K. M. Bijli, F. Fazal, M. Minhajuddin, and A. Rahman Activation of Syk by Protein Kinase C-{delta} Regulates Thrombin-induced Intercellular Adhesion Molecule-1 Expression in Endothelial Cells via Tyrosine Phosphorylation of RelA/p65 J. Biol. Chem., May 23, 2008; 283(21): 14674 - 14684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ulanova, S. Asfaha, G. Stenton, A. Lint, D. Gilbertson, A. Schreiber, and D. Befus Involvement of Syk protein tyrosine kinase in LPS-induced responses in macrophages Innate Immunity, April 1, 2007; 13(2): 117 - 125. [Abstract] [PDF]
|
|
|
|
 |
|
 Z.-Y. Huang, D. R. Barreda, R. G. Worth, Z. K. Indik, M.-K. Kim, P. Chien, and A. D. Schreiber Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis J. Leukoc. Biol., December 1, 2006; 80(6): 1553 - 1562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ulanova, L. Puttagunta, M. Marcet-Palacios, M. Duszyk, U. Steinhoff, F. Duta, M.-K. Kim, Z. K. Indik, A. D. Schreiber, and A. D. Befus Syk tyrosine kinase participates in {beta}1-integrin signaling and inflammatory responses in airway epithelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L497 - L507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Y. Huang, S. Hunter, M.-K. Kim, P. Chien, R. G. Worth, Z. K. Indik, and A. D. Schreiber The monocyte Fc{gamma} receptors Fc{gamma}RI/{gamma} and Fc{gamma}RIIA differ in their interaction with Syk and with Src-related tyrosine kinases J. Leukoc. Biol., August 1, 2004; 76(2): 491 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hewins, J. M. Williams, M. J.O. Wakelam, and C. O.S. Savage Activation of Syk in Neutrophils by Antineutrophil Cytoplasm Antibodies Occurs via Fc{gamma} Receptors and CD18 J. Am. Soc. Nephrol., March 1, 2004; 15(3): 796 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. Rosse, P. Hillmen, and A. D. Schreiber Immune-Mediated Hemolytic Anemia Hematology, January 1, 2004; 2004(1): 48 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yamamoto, K. Takeshita, M. Shichijo, T. Kokubo, M. Sato, K. Nakashima, M. Ishimori, H. Nagai, Y.-F. Li, T. Yura, et al. The Orally Available Spleen Tyrosine Kinase Inhibitor 2-[7-(3,4-Dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]nicotinamide Dihydrochloride (BAY 61-3606) Blocks Antigen-Induced Airway Inflammation in Rodents J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 1174 - 1181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dauvillier, P. Merida, M. Visintin, A. Cattaneo, C. Bonnerot, and P. Dariavach Intracellular Single-Chain Variable Fragments Directed to the Src Homology 2 Domains of Syk Partially Inhibit Fc{epsilon}RI Signaling in the RBL-2H3 Cell Line J. Immunol., September 1, 2002; 169(5): 2274 - 2283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Stenton, M. Ulanova, R. E. Dery, S. Merani, M.-K. Kim, M. Gilchrist, L. Puttagunta, S. Musat-Marcu, D. James, A. D. Schreiber, et al. Inhibition of Allergic Inflammation in the Airways Using Aerosolized Antisense to Syk Kinase J. Immunol., July 15, 2002; 169(2): 1028 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamada, S. Fujieda, S. Yanagi, H. Yamamura, R. Inatome, H. Yamamoto, H. Igawa, and H. Saito IL-1 Induced Chemokine Production Through the Association of Syk with TNF Receptor-Associated Factor-6 in Nasal Fibroblast Lines J. Immunol., July 1, 2001; 167(1): 283 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kepley, L. Youssef, R. P. Andrews, B. S. Wilson, and J. M. Oliver Multiple Defects in Fc{epsilon}RI Signaling in Syk-Deficient Nonreleaser Basophils and IL-3-Induced Recovery of Syk Expression and Secretion J. Immunol., November 15, 2000; 165(10): 5913 - 5920. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
