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RGS2 repression increases susceptibility of mice to interleukin‐ 13‐induced airway hyperresponsiveness
Author(s) -
Xie Yan,
Jiang Haihong,
Abel Peter W.,
Casale Thomas B.,
Panettieri Reynold A.,
Tu Yaping
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1095.8
Subject(s) - rgs2 , knockout mouse , bronchial hyperresponsiveness , immunology , medicine , cytokine , airway hyperresponsiveness , western blot , psychological repression , asthma , interleukin 13 , fibrosis , endocrinology , interleukin , receptor , biology , g protein , lung , respiratory disease , gene expression , gene , biochemistry , gtpase activating protein
G‐protein coupled receptors (GPCRs) are important regulators of cells involved in asthma. We recently reported that RGS2, a selective modulator of G q ‐coupled GPCRs, is a key regulator of airway hyperresponsiveness (AHR), the pathophysiologic hallmark of asthma. Since immunohistochemistry staining showed 50% repression of RGS2 protein in bronchial epithelium and smooth muscle of asthma patients as compared to non‐asthmatics, we further investigated the pathological importance of RGS2 repression in asthma. Th2 cytokine interleukin‐13 (IL‐13) is necessary and sufficient to induce AHR in mice. We found that intranasal administration of IL‐13 decreased RGS2 expression in airways and caused AHR in mice, assessed by Western blot and invasive tracheostomy. Although both hetero‐ and homozygous naïve RGS2 knockout (KO) mice exhibit spontaneous AHR, IL‐13 treatment further augmented AHR in RGS2 KO mice. Interestingly, deletion of RGS2 gene significantly enhanced IL‐13‐ induced airway remodeling, including increased peribronchial fibrosis and smooth muscle in mice. Thus, we speculate that RGS2 is an important gene regulating AHR, and RGS2 repression increases susceptibility of mice to IL‐13‐induced AHR in part through the promotion of airway remodeling. American Asthma Foundation (to Y.T.), Nebraska LB595 and 692 (to Y.T. and T.B.C.), NIH R01 HL097796 and P30 ES013508 (to R.A.P.).