IL-13 regulates cilia loss and foxj1 expression in human airway epithelium.
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.
Gomperts
Brigitte N
BN
Department of Pediatrics and Mattel Children's Hospital, University of California Los Angeles, Los Angeles, California 90095, USA. bgomperts@mednet.ucla.edu
Kim
Linda J
LJ
Flaherty
Scott A
SA
Hackett
Brian P
BP
D000818:Animals; D002923:Cilia / Q000187:drug effects* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D014162:Transfection; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D051858:Forkhead Transcription Factors; D018793:Interleukin-13; D050800:STAT6 Transcription Factor; D000099149:Ezrin; C106349:FOXJ1 protein, human; C494101:STAT6 protein, human