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Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California, San Francisco, CA 94143
Goblet cell metaplasia and mucus hypersecretion are important
features in the pathogenesis of asthma. The cytokine IL-4 has been
shown to play a role in animal models of asthma, where it induces Th2
lymphocyte differentiation and B lymphocyte IgE class switch. IL-4 has
also been implicated in the differentiation of goblet cells via effects
on lymphocytes and eosinophils. In this study we hypothesized that IL-4
induces airway epithelial cell mucin gene expression and mucous
glycoconjugate production by direct action on these cells. In vitro,
cultured airway epithelial cells (NCI-H292) expressed IL-4R
constitutively, and IL-4 (10 ng/ml) induced MUC2 gene expression and
mucous glycoconjugate production. In vivo, mouse airway epithelial
cells expressed IL-4R constitutively, and IL-4 (250 ng) increased MUC5
gene expression and Alcian blue/periodic acid-Schiff-positive staining
at 24 h; IL-4 did not increase inflammatory cell numbers in airway
tissue or in bronchoalveolar lavage. TNF-
and IL-1ß levels in
bronchoalveolar lavage were not increased in response to IL-4
instillation. These results indicate that airway epithelial cells
express IL-4R constitutively and that IL-4 directly induces the
differentiation of epithelium into mucous glycoconjugate-containing
goblet cells.
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J. Deng, V. P. Yeung, D. Tsitoura, R. H. DeKruyff, D. T. Umetsu, and S. Levy Allergen-Induced Airway Hyperreactivity Is Diminished in CD81-Deficient Mice J. Immunol., November 1, 2000; 165(9): 5054 - 5061. [Abstract] [Full Text] [PDF]
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D. C. Webb, A. N. J. McKenzie, A. M. L. Koskinen, M. Yang, J. Mattes, and P. S. Foster Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity J. Immunol., July 1, 2000; 165(1): 108 - 113. [Abstract] [Full Text] [PDF]
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M. Wills-Karp Trophic Slime, Allergic Slime Am. J. Respir. Cell Mol. Biol., June 1, 2000; 22(6): 637 - 639. [Full Text]
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P. G. KNOTT, P. R. GATER, and C. P. BERTRAND Airway Inflammation Driven by Antigen-specific Resident Lung CD4+ T Cells in alpha beta -T Cell Receptor Transgenic Mice Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1340 - 1348. [Abstract] [Full Text]
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M. Zuhdi Alimam, F. M. Piazza, D. M. Selby, N. Letwin, L. Huang, and M. C. Rose Muc-5/5ac Mucin Messenger RNA and Protein Expression Is a Marker of Goblet Cell Metaplasia in Murine Airways Am. J. Respir. Cell Mol. Biol., March 1, 2000; 22(3): 253 - 260. [Abstract] [Full Text]
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G. P. ANDERSON Interactions between Corticosteroids and beta -Adrenergic Agonists in Asthma Disease Induction, Progression, and Exacerbation Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): S188 - 196. [Full Text] [PDF]
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L. Cohn, R. J. Homer, N. Niu, and K. Bottomly T Helper 1 Cells and Interferon {gamma} Regulate Allergic Airway Inflammation and Mucus Production J. Exp. Med., November 1, 1999; 190(9): 1309 - 1318. [Abstract] [Full Text] [PDF]
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N. A. Lee and J. J. Lee The Macroimportance of the Pulmonary Immune Microenvironment Am. J. Respir. Cell Mol. Biol., September 1, 1999; 21(3): 298 - 302. [Full Text]
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M. Perrais, P. Pigny, M.-P. Ducourouble, D. Petitprez, N. Porchet, J.-P. Aubert, and I. Van Seuningen Characterization of Human Mucin Gene MUC4 Promoter. IMPORTANCE OF GROWTH FACTORS AND PROINFLAMMATORY CYTOKINES FOR ITS REGULATION IN PANCREATIC CANCER CELLS J. Biol. Chem., August 10, 2001; 276(33): 30923 - 30933. [Abstract] [Full Text] [PDF]
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