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Proliferation of the Airway Epithelium in Asthma*: Are Inflammatory Cells Required?

Brian W. Booth, BS; Dawn C. Newcomb, BS; Shaun A. McKane, BVSc, BSc(vet), PhD; Anne L. Crews, MS; Kenneth B. Adler, PhD; James C. Bonner, PhD; Linda D. Martin, PhD
Author and Funding Information

From North Carolina State University (Mr. Booth, Mss. Newcomb and Crews, and Drs. McKane, Adler, and Martin), Raleigh, NC; and NIEHS (Dr. Bonner), Research Triangle Park, NC.

Correspondence to: Linda D. Martin, PhD, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St, Raleigh, NC 27606; e-mail: linda_martin@ncsu.edu



Chest. 2003;123(3_suppl):384S-385S. doi:10.1378/chest.123.3_suppl.384S
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Asthma is associated with a T helper type 2 phenotype in which interleukin (IL)-4, IL-5, and IL-13 predominate. In addition, the long-term presence of these inflammatory mediators is thought to lead to airway structural changes that are collectively referred to as airway remodeling. Data from our laboratory, and those of others, have suggested a role for IL-13 in the development of mucous cell hyperplasia that is associated with such remodeling. Others also have suggested a role for inflammatory cells such as neutrophils in mediating this process. Using normal human bronchial epithelial (NHBE) cells differentiated in vitro, we have shown recently that IL-13 (10 ng/mL for 24 h) induces the proliferation of NHBE cells via a mechanism that is dependent on the IL-13-induced release of transforming growth factor (TGF)-α by the epithelial cells. This epithelium-derived TGF-α then acts in an autocrine/paracrine manner to bind the epidermal growth factor receptor (EGFR) on these NHBE cells, enhancing proliferation. Specifically, soluble TGF-α is released by NHBE cells in response to IL-13 exposure (1 h), and the immunohistochemical analysis of cells exposed to IL-13 (after 1 and 4 h) has revealed a lack of membrane-bound TGF-α when compared to control cells. The IL-13-induced proliferative response can be blocked in a concentration-dependent manner by AG1478 (0.1, 1, and 5 μg/mL), which is a specific inhibitor of EGFR tyrosine kinase activity, and is eliminated by neutralizing TGF-α antibodies, while control antibodies (ie, anti-platelet-derived growth factor, epidermal growth factor [EGF], and heparin-binding EGF) have no effect.

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