title: Estradiol increases mucus synthesis in bronchial epithelial cells.
abstract: Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis) and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI). Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining) in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β) antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT) in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0) cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6) mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium.
authors: The UBC James Hogg Research Centre, Providence Heart + Lung Centre & Department of Medicine, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
authors: Anthony
authors: A
authors: Tam
authors: The UBC James Hogg Research Centre, Providence Heart + Lung Centre & Department of Medicine, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
authors: Samuel
authors: S
authors: Wadsworth
authors: The UBC James Hogg Research Centre, Providence Heart + Lung Centre & Department of Medicine, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
authors: Delbert
authors: D
authors: Dorscheid
authors: The UBC James Hogg Research Centre, Providence Heart + Lung Centre & Department of Medicine, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
authors: Shu-Fan Paul
authors: SF
authors: Man
authors: The UBC James Hogg Research Centre, Providence Heart + Lung Centre & Department of Medicine, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
authors: Don D
authors: DD
authors: Sin
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000166:cytology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020397:Goblet Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010503:Periodic Acid-Schiff Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D047629:Estrogen Receptor beta; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D004958:Estradiol; D005647:Fucosyltransferases