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Cigarette smoke condensate inhibits dexamethasone‐induced glucocorticoid receptor nuclear translocation in lung epithelial cells
Author(s) -
Xu Haishan,
Chu Shijian
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.782.1
Subject(s) - dexamethasone , glucocorticoid receptor , epithelial sodium channel , glucocorticoid , tmprss2 , endocrinology , medicine , chemistry , chromosomal translocation , downregulation and upregulation , corticosteroid , nuclear receptor , gene , transcription factor , biochemistry , organic chemistry , disease , covid-19 , infectious disease (medical specialty) , sodium
Glucocorticoids are used in the treatment of pulmonary edema, asthma and COPD. Previousinvestigations have demonstrated that the epithelial Na + channel (ENaC) α‐subunit promoter possesses a glucocorticoid regulatory element, and is upregulated by glucocorticoids. Cigarette smoking is associated with corticosteroid resistance observed in patients with asthma and COPD. In this study, we aim to investigate effects of cigarette smoke condensate (CSC) on glucocorticoid‐dependent α‐ENaC gene expression and its possible mechanism. We found that dexamethasone (DEX) treatment resulted in significantly increased levels of α‐ENaC and nuclear glucocorticoid receptor (GR) in lung epithelial cells. Pre‐ and co‐treatment with CSC inhibited DEX‐induced α‐ENaC expression, but GR expression at both mRNA and protein levels was not affected. Furthermore, in cells pretreated with CSC, DEX was unable to increase nuclear GR to the full scale and cytoplasmic GR was proportionally increased. Our results demonstrate that (1) CSC dose‐dependently suppresses DEX‐induced α‐ENaC expression; (2) CSC does not inhibit GR expression and (3) CSC inhibits DEX‐induced GR nuclear translocation. These results suggest that reduced GR nuclear translocation may be partially responsible for cigarette smoking associated corticosteroid resistance. This work was supported by a grant from the Department of Veterans Affairs.