Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema.

Authors: Roh, GS  Yi, CO  Cho, YJ  Jeon, BT  Nizamudtinova, IT  Kim, HJ  Kim, JH  Oh, YM  Huh, JW  Lee, JH  Hwang, YS  Lee, SD  Lee, JD 
Citation: Roh GS, etal., Am J Physiol Lung Cell Mol Physiol. 2010 Aug;299(2):L184-91. Epub 2010 May 14.
Pubmed: (View Article at PubMed) PMID:20472710
DOI: Full-text: DOI:10.1152/ajplung.00303.2009

Chronic airway inflammation is a characteristic feature of destructive cigarette smoking (CS)-induced lung disease, particularly in patients with emphysema. Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is widely used to treat inflammation. However, the exact mechanisms underlying this drug's anti-inflammatory effects have not yet been determined in pulmonary emphysema. Here, we explore whether celecoxib attenuates CS-induced inflammation in rat lungs. Rats were exposed to smoke and received celecoxib via intragastric feeding daily for 20 wk. We found that celecoxib inhibited interalveolar wall distance and pulmonary inflammation in the lungs of CS-treated rats. Celecoxib inhibited serum NO production, iNOS, COX-2 expression, and PGE(2) production in CS-treated lung tissues. Our immunohistochemical data showed that CS-induced CD68 and COX-2 expression were inhibited by celecoxib. Furthermore, celecoxib attenuated the activation of phospho-IkappaBalpha and NF-kappaB in CS-treated rat lung. In addition, there was an inhibitory effect of celecoxib on the COX-2 expression and NF-kappaB activation in LPS-stimulated RAW 264.7 macrophages. Celecoxib also attenuated NF-kappaB activation in COX-2 siRNA-transfected RAW 264.7 macrophages. Thus, our findings suggest that the anti-inflammatory effects of celecoxib are mediated by its effects on NF-kappaB-regulated gene expression, which ultimately reduces the progression of CS-induced pulmonary emphysema.

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CRRD ID: 4891488
Created: 2011-01-17
Species: All species
Last Modified: 2011-01-17
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.