| First Author | Anagnostopoulou P | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 10 | Pages | 3629-34 |
| PubMed ID | 22945630 | Mgi Jnum | J:191668 |
| Mgi Id | MGI:5462295 | Doi | 10.1172/JCI60429 |
| Citation | Anagnostopoulou P, et al. (2012) SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation. J Clin Invest 122(10):3629-34 |
| abstractText | Asthma is a chronic condition with unknown pathogenesis, and recent evidence suggests that enhanced airway epithelial chloride (Cl-) secretion plays a role in the disease. However, the molecular mechanism underlying Cl- secretion and its relevance in asthma pathophysiology remain unknown. To determine the role of the solute carrier family 26, member 9 (SLC26A9) Cl- channel in asthma, we induced Th2-mediated inflammation via IL-13 treatment in wild-type and Slc26a9-deficient mice and compared the effects on airway ion transport, morphology, and mucus content. We found that IL-13 treatment increased Cl- secretion in the airways of wild-type but not Slc26a9-deficient mice. While IL-13-induced mucus overproduction was similar in both strains, treated Slc26a9-deficient mice exhibited airway mucus obstruction, which did not occur in wild-type controls. In a study involving healthy children and asthmatics, a polymorphism in the 3' UTR of SLC26A9 that reduced protein expression in vitro was associated with asthma. Our data demonstrate that the SLC26A9 Cl- channel is activated in airway inflammation and suggest that SLC26A9-mediated Cl- secretion is essential for preventing airway obstruction in allergic airway disease. These results indicate that SLC26A9 may serve as a therapeutic target for airway diseases associated with mucus plugging. |
