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PMID: 17541011 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

IL-13 regulates cilia loss and foxj1 expression in human airway epithelium.

American journal of respiratory cell and molecular biology ·Vol. 37 ·No. 3 ·2007-09-00 ·Pages 339-46

Gomperts BN, Kim LJ, Flaherty SA, Hackett BP

Abstract

Mucociliary clearance is essential to the defense mechanisms of the respiratory system. Loss of normal mucociliary clearance contributes to the pathogenesis of genetic and acquired lung diseases. Treatment of cultured differentiated human airway epithelial tissue with IL-13 resulted in a loss of ciliated epithelial cells and an increase in mucus-secreting cells. The loss of ciliated cells was characterized by mislocation of basal bodies and loss of ezrin from the apical cell compartment. In addition to the loss of ciliated cells and increase in mucous cells after IL-13 treatment, cells with characteristics of both ciliated and mucous cells were observed in the airway epithelium. In association with the decrease in ciliated cells after IL-13 treatment, there was noted a decrease in foxj1 expression in the airway epithelium, characterized by a decrease in the number of foxj1-expressing cells. Within the foxj1 promoter, a STAT-binding element was identified and inhibition of foxj1 expression by STAT-6 and IL-13 was demonstrated. These findings suggest molecular and cellular mechanisms for cilia loss in pulmonary disease. Inhibition of foxj1 expression results in loss of apical localization of ezrin and basal bodies with subsequent loss of axonemal structures. These findings have important implications for the pathogenesis and treatment of airway diseases.

MeSH Terms
Animals Cilia/drug effects,pathology Cytoskeletal Proteins/genetics Forkhead Transcription Factors/genetics Gene Expression Regulation/drug effects Humans Interleukin-13/pharmacology Mice Models, Biological Promoter Regions, Genetic Respiratory System/drug effects,metabolism,pathology STAT6 Transcription Factor/genetics,metabolism Tissue Culture Techniques Transfection
Chemicals
Cytoskeletal Proteins FOXJ1 protein, human Forkhead Transcription Factors Interleukin-13 STAT6 Transcription Factor STAT6 protein, human ezrin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gomperts Brigitte N
Department of Pediatrics and Mattel Children's Hospital, University of California Los Angeles, Los Angeles, California 90095, USA. [email protected]
Kim Linda J
Flaherty Scott A
Hackett Brian P
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Article Info
Journal
American journal of respiratory cell and molecular biology
Abbr.
Am J Respir Cell Mol Biol
ISSN
1044-1549
DOI
10.1165/rcmb.2006-0400OC
Email
[email protected]
Published
2007-09-00
Epub
2007-00-31
Pages
339-46
Language
English
Region
United States
NLM ID
8917225
PMCID
PMC2720122
Subset
IM
Grants
NICHD NIH HHS · T32-HD07507 · United States
NHLBI NIH HHS · K08-HL074229 · United States
NICHD NIH HHS · R01-HD37036 · United States
NICHD NIH HHS · K12-HD00850 · United States
NICHD NIH HHS · T32-HD041925 · United States
External Links
PubMed source DOI: 10.1165/rcmb.2006-0400OC PMC Full Text View journal details
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