BACKGROUND AND OBJECTIVES: Airway hypersecretion is a frequent feature of several respiratory tract diseases including rhinitis, sinusitis, and otitis media. Efforts are being made in several laboratories to elucidate mechanisms involved in the regulation of secretion. There are several factors which modulate expression of the secretory phenotype, such as retinoic acid (RA), triiodothyronine, steroid, and extracellular matrix. We have been interested in elucidating the role of retinoids in regulating differentiation of mucin and non-mucin secretions. MATERIALS AND METHODS: Retinoic acid was removed from the culture media of normal human tracheobronchial epithelial cells grown in the air-liquid interface cultures. The effects on cell phenotype and mucin, lysozyme (LZ), and the secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. RESULTS: Removal of RA from the media induced squamous differentiation and caused a drastic decrease in mucin secretion and a decrease in expression of the mucin genes, MUC2 and MUC5AC. Lysozyme and SLPI secretions were increased in RA-depleted cultures. Paradoxically, LZ mRNA was decreased, while the SLPI mRNA levels were increased. A most intriguing finding was the paradoxical response of LZ to RA-depletion. The reason for this apparant incongruity between mRNA and protein levels is currently under investigation. CONCLUSION: Our studies show that RA is an important factor for mucous differentiation.
Culture Media ; Epithelial Cells ; Epithelium* ; Extracellular Matrix ; Gene Expression* ; Humans* ; Mucins* ; Muramidase ; Otitis Media ; Phenotype ; Respiratory Tract Diseases ; Retinoids ; Rhinitis ; RNA, Messenger ; Secretory Leukocyte Peptidase Inhibitor ; Sinusitis ; Tretinoin* ; Triiodothyronine

BACKGROUND AND OBJECTS: We have been interested in elucidating the role of hormones and growth factors in regulating differentiation and mucin and non-mucin secretions. Our purpose is to investigate the effects of each supplement contained in the culture medium for mucin and non-mucin secretions. MATERIALS AND METHODS: Individual factors were removed from the culture media of normal human tracheobronchial epithelial (NHTBE) cells grown in air-liquid interface cultures. The effects on the cell phenotype, mucin, lysozyme (LZ), and secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. RESULTS: Deletion of hydrocortisone, epinephrine, transferrin or amphotericin-gentamycin from the media had no reproducible effects; Deletion of insulin was incompatible with culture growth. Removal of triiodothyronine selectively increased mucin secretion, but did not affect the gene expression. However, MUC5AC mRNA levels were reproducibly increased, suggesting that the expressions of these two mucin genes were differentially regulated. LZ and SLPI secretion levels were not significantly affected by the deletion of triiodothyronine from the culture media. The LZ mRNA levels were increased in the absence of triiodothyronine whereas the SLPI transcript levels were not affected. Omission of the attachment substratum and the type 1 collagen gel resulted in a significant increase in all 3 secretory products. MUC2 and MUC5AC steady state mRNA levels were not consistently affected. In contrast, LZ and SLPI gene expressions were reproducibly increased. CONCLUSION: This study shows that individual factors in the epithelial environment can regulate the expression of specific secretory cell gene products in a highly selective manner.
Collagen Type I ; Collagen* ; Culture Media ; Epinephrine ; Epithelium* ; Extracellular Matrix ; Gene Expression* ; Humans* ; Hydrocortisone ; Insulin ; Intercellular Signaling Peptides and Proteins ; Mucins* ; Muramidase ; Phenotype ; RNA, Messenger ; Secretory Leukocyte Peptidase Inhibitor ; Transferrin ; Triiodothyronine*