Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Respir Crit Care Med. 2002 Apr 1;165(7):1015-21.

Inhibition of antigen-induced eosinophilia and airway hyperresponsiveness by antisense oligonucleotides directed against the common beta chain of IL-3, IL-5, GM-CSF receptors in a rat model of allergic asthma.

Author information

1
CHUM Research Center, Notre-Dame Hospital, University of Montreal, Montreal, Quebec, Canada.

Abstract

Airway obstruction, hyperresponsiveness, and the accumulation and persistence within the airways of inflammatory cells characterize asthma. Interleukin (IL)-3, granulocyte macrophage colony- stimulating factor (GM-CSF), and IL-5 are among several cytokines that have been shown to be increased in asthma and to contribute to atopic inflammation. They mediate their effect via receptors that have a common beta subunit (beta(c)). We hypothesized that blocking of this common beta(c) would impair the airway response to antigen. We report that an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) found to specifically inhibit transcription of the beta(c) in rat bone marrow cells also caused inhibition of beta(c) mRNA expression and of immunoreactive cells within the lungs of Brown Norway (BN) rats when injected intratracheally (p < 0.01). Inhibition of beta(c) significantly reduced (p < 0.01) experimentally induced eosinophilia in vivo in ovalbumin (OVA)-sensitized BN rats after antigen challenge. Furthermore, when compared with mismatch-treated rats, beta(c) AS-ODN caused inhibition of antigen-induced airway hyperresponsiveness to leukotriene D4. Taken together, our findings demonstrate that the common beta(c) of IL-3, IL-5, and GM-CSF receptors is involved in the eosinophil influx and airway hyperresponsiveness that follow OVA challenge and underscore the potential utility of a topical antisense approach targeting beta

PMID:
11934731
DOI:
10.1164/ajrccm.165.7.2109095
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Support Center