{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T07:53:17Z","timestamp":1774079597443,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Invasive cell phenotypes have been demonstrated in malignant transformation, but not in other diseases, such as asthma. Cellular invasiveness is thought to be mediated by transforming growth factor (TGF)-\u03b21 and matrix metalloproteinases (MMPs). IL-13 is a key TH2 cytokine that directs many features of airway remodeling through TGF-\u03b21 and MMPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We hypothesized that, in human asthma, IL-13 stimulates increased airway fibroblast invasiveness via TGF-\u03b21 and MMPs in asthma compared with normal controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fibroblasts were cultured from endobronchial biopsies in 20 subjects with mild asthma (FEV1: 90 \u00b1 3.6% pred) and 17 normal control subjects (FEV1: 102 \u00b1 2.9% pred) who underwent bronchoscopy. Airway fibroblast invasiveness was investigated using Matrigel chambers. IL-13 or IL-13 with TGF-\u03b21 neutralizing antibody or pan-MMP inhibitor (GM6001) was added to the lower chamber as a chemoattractant. Flow cytometry and immunohistochemistry were performed in a subset of subjects to evaluate IL-13 receptor levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>IL-13 significantly stimulated invasion in asthmatic airway fibroblasts, compared with normal control subjects. Inhibitors of both TGF-\u03b21 and MMPs blocked IL-13\u2013induced invasion in asthma, but had no effect in normal control subjects. At baseline, in airway tissue, IL-13 receptors were expressed in significantly higher levels in asthma, compared with normal control subjects. In airway fibroblasts, baseline IL-13R\u03b12 was reduced in asthma compared with normal control subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IL-13 potentiates airway fibroblast invasion through a mechanism involving TGF-\u03b21 and MMPs. IL-13 receptor subunits are differentially expressed in asthma. These effects may result in IL-13\u2013directed airway remodeling in asthma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201009-1452oc","type":"journal-article","created":{"date-parts":[[2011,3,25]],"date-time":"2011-03-25T22:13:17Z","timestamp":1301091197000},"page":"1625-1632","source":"Crossref","is-referenced-by-count":50,"title":["Airway Fibroblasts in Asthma Manifest an Invasive Phenotype"],"prefix":"10.1093","volume":"183","author":[{"given":"Jennifer L.","family":"Ingram","sequence":"first","affiliation":[{"name":"Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly J.","family":"Huggins","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony D.","family":"Church","sequence":"additional","affiliation":[{"name":"Department of 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