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Aerosolized Syk Antisense Suppresses Syk Expression, Mediator Release from Macrophages, and Pulmonary Inflammation

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Author(s)
Grant R. StentonMoo-Kyung KimOsamu NoharaChin-Fu ChenNadir HirjiFiona L. WillsMark GilchristPyoung-Han HwangJong-Gu ParkWarren FinlayRichard L. JonesA. Dean BefusAlan D. Schreiber
Keimyung Author(s)
Park, Jong Gu
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Journal of Immunology
Issued Date
2000
Volume
164
Issue
7
Abstract
Syk protein tyrosine kinase (PTK) is involved in signaling in leukocytes. In macrophages, Fcγ-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 Fcγ-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, Fcγ-receptor-induced IL-1β 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.
Keimyung Author(s)(Kor)
박종구
Publisher
School of Medicine
Citation
Grant R. Stenton et al. (2000). Aerosolized Syk Antisense Suppresses Syk Expression, Mediator Release from Macrophages, and Pulmonary Inflammation. Journal of Immunology, 164(7), 3790–3797. doi: 10.4049/jimmunol.164.7.3790
Type
Article
ISSN
0022-1767
DOI
10.4049/jimmunol.164.7.3790
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34054
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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