Document Detail


A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion.
MedLine Citation:
PMID:  9115759     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mucus hypersecretion and plugging of lower respiratory tract airways contributes to the morbidity and mortality associated with asthma. Interleukin (IL)-4 plays a putative role in some forms of asthma. Thus, transgenic mice that overexpress murine IL-4 selectively within the lung were used to study the effect of IL-4 on mucus glycoprotein gene expression and mucin release. Histologic examination of lung sections from IL-4 mice revealed that nonciliated epithelial cells from conducting airways were hypertrophic, due at least in part to the accumulation of mucus glycoprotein. The cytoplasm of these cells stained positively for glycoproteins using mucicarmine, alcian blue (AB), and periodic acid-Schiff (PAS). Ciliated cells were also enlarged but did not show any mucin-specific staining. Inclusion granules typically found in nonciliated (Clara) cells of control mice were absent in the IL-4 transgenic mice. Northern blot analysis of total RNA from lung tissue revealed that the expression of the MUC5AC, but not MUC2, mucin gene was distinctly upgraded in IL-4 transgenic mice compared to transgene-negative controls. In addition, a 5- to 10-fold increase in AB- and PAS-positive material was found in lavage fluid from IL-4 overexpressing mice compared to transgene-negative controls. Thus, the overexpression of IL-4 locally within the lung enhances mucus glycoprotein synthesis by altering gene expression, results in the accumulation of mucus glycoprotein in nonciliated epithelial cells, and induces the release of mucus into the airway lumen. We therefore hypothesize that the overproduction of mucus seen in some patients with asthma may be a direct result of the action of IL-4 within the inflamed lung.
Authors:
U A Temann; B Prasad; M W Gallup; C Basbaum; S B Ho; R A Flavell; J A Rankin
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  16     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-04-23     Completed Date:  1997-04-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  471-8     Citation Subset:  IM    
Affiliation:
Pulmonary and Critical Care Medicine, West Haven VAMC, Connecticut 06516, USA.
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MeSH Terms
Descriptor/Qualifier:
Alcian Blue
Animals
Bronchoalveolar Lavage Fluid
Gene Expression Regulation / physiology*
Interleukin-4 / physiology*
Lung / metabolism,  secretion,  ultrastructure
Mice
Mice, Transgenic
Microscopy, Electron
Mucins / genetics*,  secretion
Periodic Acid-Schiff Reaction
Grant Support
ID/Acronym/Agency:
HL24136/HL/NHLBI NIH HHS; HL43762/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Mucins; 12040-44-7/Alcian Blue; 207137-56-2/Interleukin-4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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