Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production

Zhou Zhu, Robert J. Homer, Zhonde Wang, Qingsheng Chen, Gregory P. Geba, Jingming Wang, Yong Zhang, Jack A. Elias

Research output: Contribution to journalArticle

Abstract

Interleukin (IL)-13 is a pleiotropic cytokine produced in large quantities by activated CD4+ Th2 lymphocytes. To define further its potential in vivo effector functions, the Clara cell 10-kDa protein promoter was used to express IL-13 selectively in the lung, and the phenotype of the resulting transgenic mice was characterized. In contrast to transgene- negative littermates, the lungs of transgene-positive mice contained an inflammatory response around small and large airways and in the surrounding parenchyma. It was mononuclear in nature and contained significant numbers of eosinophils and enlarged and occasionally multinucleated macrophages. Airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot-Leyden-like crystals, and subepithelial airway fibrosis were also prominently noted. Eotaxin protein and mRNA were also present in large quantities in the lungs of the transgene- positive, but not the transgene-negative, mice. IL-4, IL-5, granulocyte- macrophage colony-stimulating factor, and monocyte chemoattractant protein-5 were not similarly detected. Physiological evaluations revealed significant increases in baseline airways resistance and airways hyperresponsiveness (AHR) to methacholine in transgene-positive animals. Thus, the targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, the deposition of Charcot- Leyden-like crystals, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR. IL-13 may play an important role in the pathogenesis of similar responses in asthma or other Th2-polarized tissue responses.

Original languageEnglish (US)
Pages (from-to)779-788
Number of pages10
JournalJournal of Clinical Investigation
Volume103
Issue number6
StatePublished - Mar 1999
Externally publishedYes

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Interleukin-13
Mucus
Transgenes
Fibrosis
Inflammation
Lung
Metaplasia
Monocyte Chemoattractant Proteins
Airway Resistance
Methacholine Chloride
Interleukin-5
Airway Obstruction
Granulocyte-Macrophage Colony-Stimulating Factor
Eosinophils
Interleukin-4
Hypertrophy
Transgenic Mice
Proteins
Asthma
Epithelial Cells

ASJC Scopus subject areas

  • Medicine(all)

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Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. / Zhu, Zhou; Homer, Robert J.; Wang, Zhonde; Chen, Qingsheng; Geba, Gregory P.; Wang, Jingming; Zhang, Yong; Elias, Jack A.

In: Journal of Clinical Investigation, Vol. 103, No. 6, 03.1999, p. 779-788.

Research output: Contribution to journalArticle

Zhu, Zhou ; Homer, Robert J. ; Wang, Zhonde ; Chen, Qingsheng ; Geba, Gregory P. ; Wang, Jingming ; Zhang, Yong ; Elias, Jack A. / Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. In: Journal of Clinical Investigation. 1999 ; Vol. 103, No. 6. pp. 779-788.
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abstract = "Interleukin (IL)-13 is a pleiotropic cytokine produced in large quantities by activated CD4+ Th2 lymphocytes. To define further its potential in vivo effector functions, the Clara cell 10-kDa protein promoter was used to express IL-13 selectively in the lung, and the phenotype of the resulting transgenic mice was characterized. In contrast to transgene- negative littermates, the lungs of transgene-positive mice contained an inflammatory response around small and large airways and in the surrounding parenchyma. It was mononuclear in nature and contained significant numbers of eosinophils and enlarged and occasionally multinucleated macrophages. Airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot-Leyden-like crystals, and subepithelial airway fibrosis were also prominently noted. Eotaxin protein and mRNA were also present in large quantities in the lungs of the transgene- positive, but not the transgene-negative, mice. IL-4, IL-5, granulocyte- macrophage colony-stimulating factor, and monocyte chemoattractant protein-5 were not similarly detected. Physiological evaluations revealed significant increases in baseline airways resistance and airways hyperresponsiveness (AHR) to methacholine in transgene-positive animals. Thus, the targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, the deposition of Charcot- Leyden-like crystals, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR. IL-13 may play an important role in the pathogenesis of similar responses in asthma or other Th2-polarized tissue responses.",
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AU - Elias, Jack A.

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