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We demonstrated previously that IL-13 induces release of transforming growth factor-\u03b1 (TGF\u03b1) from human bronchial epithelial cells, with proliferation of these cells mediated by the autocrine\/paracrine action of this growth factor. TGF\u03b1 exists as an integral membrane protein and requires proteolytic processing to its mature form, with a disintegrin and metalloproteinase (ADAM)17 responsible for this processing in a variety of tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, normal human bronchial epithelial (NHBE) cells grown in air\/liquid interface (ALI) culture were used to examine the mechanisms whereby IL-13 induces release of TGF\u03b1 and cellular proliferation. Inhibitors and antisense RNA were used to examine the role of ADAM17 in these processes, while IL-13-induced changes in the intracellular expression of TGF\u03b1 and ADAM17 were visualized by confocal microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL-13 was found to induce proliferation of NHBE cells, and release of TGF\u03b1, in an ADAM17-dependent manner; however, this IL-13-induced proliferation did not appear to result solely from ADAM17 activation. Rather, IL-13 induced a change in the location of TGF\u03b1 expression from intracellular to apical regions of the NHBE cells. The apical region was also found to be a site of significant ADAM17 expression, even prior to IL-13 stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Results from this study indicate that ADAM17 mediates IL-13-induced proliferation and TGF\u03b1 shedding in NHBE cells. Furthermore, they provide the first example wherein a cytokine (IL-13) induces a change in the intracellular expression pattern of a growth factor, apparently inducing redistribution of intracellular stores of TGF\u03b1 to the apical region of NHBE cells where expression of ADAM17 is prominent. Thus, IL-13-induced, ADAM17-mediated release of TGF\u03b1, and subsequent epithelial cell proliferation, could contribute to the epithelial hypertrophy, as well as other features, associated with airway remodeling in allergic asthma.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1465-9921-8-51","type":"journal-article","created":{"date-parts":[[2007,7,10]],"date-time":"2007-07-10T06:13:57Z","timestamp":1184048037000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["IL-13-induced proliferation of airway epithelial cells: mediation by intracellular growth factor mobilization and ADAM17"],"prefix":"10.1186","volume":"8","author":[{"given":"Brian W","family":"Booth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Sandifer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika L","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda D","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,7,9]]},"reference":[{"key":"589_CR1_589","doi-asserted-by":"publisher","first-page":"S39","DOI":"10.1164\/ajrccm.164.supplement_2.2106065","volume":"164","author":"DM McDonald","year":"2001","unstructured":"McDonald DM: Angiogenesis and remodeling of airway vasculature in chronic inflammation. 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