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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-11-5
pubmed:abstractText
Interleukin (IL)-9 is a T helper (Th) 2 cytokine recently implicated as an essential factor in determining susceptibility to asthma. Transgenic mice overexpressing IL-9 exhibit many features that are characteristic of human asthma. To better understand the mechanism by which IL-9 mediates the various biologic activities in asthma, we performed suppressive subtraction hybridization with whole lung from IL-9 transgenic and control mice. Here we report the identification of mCLCA3, a calcium-activated chloride channel that was specifically induced in the lung epithelium of IL-9 transgenic mice. Expression of mCLCA3 could also be induced by intratracheal administration of IL-9 or other Th2 cytokines (IL-4, IL-13), but not by interferon-gamma. Moreover, expression of mCLCA3 was induced in the lung of antigen-exposed mice, and this induction could be suppressed by neutralizing IL-9 antibody treatment, indicating IL-9 is both necessary and sufficient to induce mCLCA3 in this experimental model of asthma. Finally, we demonstrate that hCLCA1 is the human counterpart to mCLCA3 and is also induced in vitro in human primary lung cells by Th2 cytokine treatment. Together, these data strongly implicate the involvement of mCLCA3 (in mice) and hCLCA1 (in humans) in the pathogenesis of Th2 cytokine-mediated asthmatic disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
486-91
pubmed:dateRevised
2004-11-18
pubmed:meshHeading
pubmed-meshheading:11694454-Amino Acid Sequence, pubmed-meshheading:11694454-Animals, pubmed-meshheading:11694454-Antibodies, Monoclonal, pubmed-meshheading:11694454-Asthma, pubmed-meshheading:11694454-Chloride Channels, pubmed-meshheading:11694454-Cloning, Molecular, pubmed-meshheading:11694454-Cytokines, pubmed-meshheading:11694454-Humans, pubmed-meshheading:11694454-In Situ Hybridization, pubmed-meshheading:11694454-Interleukin-9, pubmed-meshheading:11694454-Lung, pubmed-meshheading:11694454-Mice, pubmed-meshheading:11694454-Mice, Inbred Strains, pubmed-meshheading:11694454-Mice, Transgenic, pubmed-meshheading:11694454-Molecular Sequence Data, pubmed-meshheading:11694454-Mucoproteins, pubmed-meshheading:11694454-Recombinant Proteins, pubmed-meshheading:11694454-Respiratory Mucosa, pubmed-meshheading:11694454-Signal Transduction, pubmed-meshheading:11694454-Th2 Cells
pubmed:year
2001
pubmed:articleTitle
Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma.
pubmed:affiliation
Genaera Institute of Molecular Medicine, Genaera Corporation, 5110 Campus Drive, Plymouth Meeting, PA 19462, USA.
pubmed:publicationType
Journal Article