| First Author | Martino MB | Year | 2013 |
| Journal | Mucosal Immunol | Volume | 6 |
| Issue | 3 | Pages | 639-54 |
| PubMed ID | 23168839 | Mgi Jnum | J:315294 |
| Mgi Id | MGI:6830028 | Doi | 10.1038/mi.2012.105 |
| Citation | Martino MB, et al. (2013) The ER stress transducer IRE1beta is required for airway epithelial mucin production. Mucosal Immunol 6(3):639-54 |
| abstractText | Inflammation of human bronchial epithelia (HBE) activates the endoplasmic reticulum (ER) stress transducer inositol-requiring enzyme 1 (IRE1)alpha, resulting in IRE1alpha-mediated cytokine production. Previous studies demonstrated ubiquitous expression of IRE1alpha and gut-restricted expression of IRE1beta. We found that IRE1beta is also expressed in HBE, is absent in human alveolar cells, and is upregulated in cystic fibrosis and asthmatic HBE. Studies with Ire1beta(-/-) mice and Calu-3 airway epithelia exhibiting IRE1beta knockdown or overexpression revealed that IRE1beta is expressed in airway mucous cells, is functionally required for airway mucin production, and this function is specific for IRE1beta vs. IRE1alpha. IRE1beta-dependent mucin production is mediated, at least in part, by activation of the transcription factor X-box binding protein-1 (XBP-1) and the resulting XBP-1-dependent transcription of anterior gradient homolog 2, a gene implicated in airway and intestinal epithelial mucin production. These novel findings suggest that IRE1beta is a potential mucous cell-specific therapeutic target for airway diseases characterized by mucin overproduction. |
