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

Zhou, YH Dong, Q Louahed, J Dragwa, C Savio, D Huang, MX Weiss, C Tomer, Y McLane, MP Nicolaides, NC Levitt, RC

Yh. Zhou et al., Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma, AM J RESP C, 25(4), 2001, pp. 486-491

34

INGLESE

Article

da verificare

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

1044-1549 → ACNP

25

4

2001

486 - 491

ISI

1044-1549(200110)25:4<486:COACCC>2.0.ZU;2-8

Interleukin (IL)-9 is a T helper (Th) 2 cytokine recently implicated as an essential factor in determining susceptibility to asthma. Transgenic mice o verexpressing IL-9 exhibit many features that are characteristic of human a sthma. To better understand the mechanism by which I L-9 mediates the vario us biologic activities in asthma, we performed suppressive subtraction hybr idization with whole lung from IL-9 transgenic and control mice. Here we re port the identification of mCLCA3, a calcium-activated chloride channel tha t 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 m ice, and this induction could be suppressed by neutralizing IL-9 antibody t reatment, 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 pr imary lung cells by Th2 cytokine treatment. Together, these data strongly i mplicate the involvement of mCLCA3 (in mice) and hCLCA1 (in humans) in the pathogenesis of Th2 cytokine-mediated asthmatic disorders.