Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma

Y. Zhou, Q. Dong, J. Louahed, C. Dragwa, D. Savio, M. Huang, C. Weiss, Y. Tomer, M. P. McLane, N. C. Nicolaides, Roy C Levitt

Research output: Contribution to journalArticle

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Abstract

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 rnCLCA3, a calcium-activated chloride channel that was specifically induced in the lung epithelium of IL-9 transgenic mice. Expression of rnCLCA3 could also be induced by intratracheal administration of IL-9 or other Th2 cytokines (IL-4, IL-13), but not by interferon-γ. 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 rnCLCA3 and is also induced in vitro in human primary lung cells by Th2 cytokine treatment. Together, these data strongly implicate the involvement of rnCLCA3 (in mice) and hCLCA 1 (in humans) in the pathogenesis of Th2 cytokine-mediated asthmatic disorders.

Original languageEnglish
Pages (from-to)486-491
Number of pages6
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume25
Issue number4
StatePublished - Nov 20 2001
Externally publishedYes

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Interleukin-9
Chloride Channels
Asthma
Cytokines
Transgenic Mice
Lung
Th2 Cells
Interleukin-13
Interleukin-4
Interferons
Theoretical Models
Epithelium
Antigens

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma. / Zhou, Y.; Dong, Q.; Louahed, J.; Dragwa, C.; Savio, D.; Huang, M.; Weiss, C.; Tomer, Y.; McLane, M. P.; Nicolaides, N. C.; Levitt, Roy C.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 25, No. 4, 20.11.2001, p. 486-491.

Research output: Contribution to journalArticle

Zhou, Y, Dong, Q, Louahed, J, Dragwa, C, Savio, D, Huang, M, Weiss, C, Tomer, Y, McLane, MP, Nicolaides, NC & Levitt, RC 2001, 'Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma', American Journal of Respiratory Cell and Molecular Biology, vol. 25, no. 4, pp. 486-491.
Zhou, Y. ; Dong, Q. ; Louahed, J. ; Dragwa, C. ; Savio, D. ; Huang, M. ; Weiss, C. ; Tomer, Y. ; McLane, M. P. ; Nicolaides, N. C. ; Levitt, Roy C. / Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma. In: American Journal of Respiratory Cell and Molecular Biology. 2001 ; Vol. 25, No. 4. pp. 486-491.
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