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- Title
Involvement of Na, K-ATPase and its inhibitors in HuR-mediated cytokine mRNA stabilization in lung epithelial cells.
- Authors
Feng, Su; Chen, Wei; Cao, Dan; Bian, Jinjun; Gong, Fang-Yuan; Cheng, Wei; Cheng, Shun; Xu, Qiang; Hua, Zi-Chun; Yin, Wu
- Abstract
Increasing evidence demonstrates that Na, K-ATPase plays an important role in pulmonary inflammation, but the mechanism remains largely unknown. In this study, we used cardiotonic steroids as Na, K-ATPase inhibitors to explore the possible involvement of Na, K-ATPase in pulmonary epithelial inflammation. The results demonstrated that mice after ouabain inhalation developed cyclooxygenase-2-dependent acute lung inflammation. The in vitro experiments further confirmed that Na, K-ATPase inhibitors significantly stimulated cyclooxygenase-2 expression in lung epithelial cells of human or murine origin, the process of which was participated by multiple cis-elements and trans-acting factors. Most importantly, we first described here that Na, K-ATPase inhibitors could evoke a significant Hu antigen R nuclear export in lung epithelial cells, which stabilized cyclooxygenase-2 mRNA by binding with a proximal AU-rich element within its 3′-untranslated region. In conclusion, HuR-mediated mRNA stabilization opens new avenues in understanding the importance of Na, K-ATPase, as well as its inhibitors in inflammation.
- Subjects
ADENOSINE triphosphatase; CYTOKINES; EPITHELIAL cells; CYCLOOXYGENASE 2; PNEUMONIA; ANTIGENS; CARDIAC glycosides; LABORATORY mice
- Publication
Cellular & Molecular Life Sciences, 2011, Vol 68, Issue 1, p109
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-010-0444-1