| First Author | Chand HS | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 436 |
| PubMed ID | 29323189 | Mgi Jnum | J:260134 |
| Mgi Id | MGI:6148367 | Doi | 10.1038/s41598-017-18884-9 |
| Citation | Chand HS, et al. (2018) IL-13 in LPS-Induced Inflammation Causes Bcl-2 Expression to Sustain Hyperplastic Mucous cells. Sci Rep 8(1):436 |
| abstractText | Exposure to lipopolysaccharides (LPS) causes extensive neutrophilic inflammation in the airways followed by mucous cell hyperplasia (MCH) that is sustained by the anti-apoptotic protein, Bcl-2. To identify inflammatory factor(s) that are responsible for Bcl-2 expression, we established an organ culture system consisting of airway epithelial tissue from the rat nasal midseptum. The highest Muc5AC and Bcl-2 expression was observed when organ cultures were treated with brochoalveolar lavage (BAL) fluid harvested from rats 10 h post LPS instillation. Further, because BAL harvested from rats depleted of polymorphonuclear cells compared to controls showed increased Bcl-2 expression, analyses of cytokine levels in lavages identified IL-13 as an inducer of Bcl-2 expression. Ectopic IL-13 treatment of differentiated airway epithelial cells increased Bcl-2 and MUC5AC expression in the basal and apical regions of the cells, respectively. When Bcl-2 was blocked using shRNA or a small molecule inhibitor, ABT-263, mucous cell numbers were reduced due to increased apoptosis that disrupted the interaction of Bcl-2 with the pro-apoptotic protein, Bik. Furthermore, intranasal instillation of ABT-263 reduced the LPS-induced MCH in bik (+/+) but not bik (-/-) mice, suggesting that Bik mediated apoptosis in hyperplastic mucous cells. Therefore, blocking Bcl-2 function could be useful in reducing IL-13 induced mucous hypersecretion. |
