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Regulation of the Secretory Phenotype of Human Airway Epithelium by Retinoic Acid, Triiodothyronine, and Extracellular Matrix

Authors
 Joo-Heon Yoon  ;  Thomas Gray  ;  Karen Guzman  ;  Ja Seok Koo  ;  Paul Nettesheim 
Citation
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol.16(6) : 724-731, 1997 
Journal Title
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 
ISSN
 1044-1549 
Issue Date
1997
MeSH
Anti-Infective Agents/metabolism ; Antineoplastic Agents/pharmacology* ; Bronchi/cytology* ; Cells, Cultured ; Collagen/pharmacology ; Dose-Response Relationship, Drug ; Epithelial Cells ; Epithelium/enzymology ; Epithelium/metabolism ; Extracellular Matrix Proteins/pharmacology* ; Gels ; Gene Expression Regulation/drug effects ; Humans ; Molecular Sequence Data ; Mucin 5AC ; Mucin-2 ; Mucins/genetics ; Muramidase/genetics ; Neoplasm Proteins/genetics ; Phenotype ; Proteinase Inhibitory Proteins, Secretory ; Proteins/genetics ; RNA, Messenger/metabolism ; Secretory Leukocyte Peptidase Inhibitor ; Serine Proteinase Inhibitors/genetics ; Trachea/cytology* ; Tretinoin/pharmacology* ; Triiodothyronine/pharmacology*
Abstract
The purpose of our studies was to identify factors which regulate the composition of airway secretions produced by normal human tracheobronchial epithelial (NHTBE) cells. Individual factors were removed from the culture media of NHTBE cells grown in air-liquid interface (ALI) cultures (which support mucociliary differentiation) and the effects on mucin, lysozyme (LZ), and secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. Deletion of hydrocortisone, epinephrine, transferrin, or gentamycin-amphotericin from the media had no reproducible effects; deletion of insulin was incompatible with culture growth. We identified 3 factors, namely retinoic acid (RA), triiodothyronine (T3) and collagen gel substratum, which had a major impact on the profile of NHTBE secretions. Removal of RA from the media caused a drastic decrease in mucin secretion and a decrease in expression of the mucin genes MUC2 and MUC5AC.LZ and SLPI secretions were increased in these cultures. Paradoxically LZ mRNA was decreased, while SLPI mRNA levels were increased. Removal of T3 selectively increased mucin secretion, MUC2 gene expression was not affected, but MUC5AC mRNA levels reproducibly increased, suggesting that the expression of these two mucin genes is differentially regulated. LZ and SLPI secretion levels were not significantly affected by deletion of T3 from the culture media; however, LZ mRNA levels were increased in the absence of T3 while SLPI transcript levels were not affected. Omission of the attachment substratum, type I collagen gel, resulted in significant increases in all 3 secretory products. MUC2 and MUC5AC steady state mRNA levels were not consistently affected. In contrast LZ and SLPI gene expression were reproducibly increased. Our studies show that individual factors in the epithelial environment can regulate expression of specific secretory cell gene products in a highly selective manner.
Full Text
https://www.atsjournals.org/doi/abs/10.1165/ajrcmb.16.6.9191474
DOI
10.1165/ajrcmb.16.6.9191474
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/177255
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