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1: Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 2):S67-70.
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Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice.

Zhu Z, Lee CG, Zheng T, Chupp G, Wang J, Homer RJ, Noble PW, Hamid Q, Elias JA.

Section of Pulmonary and Critical Care Medicine, and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8057, USA.

Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been adequately defined. Because exaggerated cytokine production is a characteristic feature of the asthmatic airway, we used constitutive and inducible overexpression transgenic systems to investigate the contributions that interleukin 11 (IL-11) and IL-13 might make to airway remodeling responses. These studies demonstrated that both cytokines produce responses in the murine airway with features similar to those in human asthmatic tissues. IL-11 caused airway fibrosis with the enhanced accumulation of interstitial collagens, myocytes, and myofibroblasts. IL-13 caused mucous metaplasia, enhanced mucin gene expression, enhanced tissue hyaluronic acid accumulation, and subepithelial fibrosis. Importantly, IL-11 was detected most readily in tissues from asthmatic subjects with severe airway remodeling that was similar to that seen in the IL-11 transgenic mice. In addition, IL-11 was shown to inhibit asthma-like inflammation while stimulating airway fibrosis. This suggests that IL-11 elaboration is, in part, an attempt at airway healing. Last, a novel triple transgenic system is described that allows transgene expression to be regulated in a true "on/off" manner. This system may be useful in defining the reversibility of transgene-induced airway remodeling responses.

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PMID: 11734470 [PubMed - indexed for MEDLINE]