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

Abstract

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.

• Authors: Gu Seob Roh, Chin-ok Yi, Yu Ji Cho, Byeong Tak Jeon, Irina Tsoy Nizamudtinova, Hye Jung Kim, Jin Hyun Kim, Yeon-Mok Oh, Jin Won Huh, Ji-Hyun Lee, Young Sil Hwang, Sang Do Lee, Jong Deog Lee
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 299 Issue 2 Pg. L184-91 (Aug 2010) ISSN: 1522-1504 [Electronic] United States
• PMID: 20472710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 protein, rat
• Cyclooxygenase 2 Inhibitors
• I-kappa B Proteins
• NF-kappa B
• Nfkbia protein, mouse
• Nfkbia protein, rat
• Pyrazoles
• Sulfonamides
• NF-KappaB Inhibitor alpha
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Celecoxib
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Celecoxib
• Cell Line
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Dinoprostone (metabolism)
• I-kappa B Proteins (metabolism)
• Inflammation (pathology)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Nitric Oxide (biosynthesis, blood)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Phosphorylation
• Pulmonary Alveoli (pathology)
• Pulmonary Emphysema (drug therapy, etiology, pathology)
• Pyrazoles (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Smoking (adverse effects)
• Sulfonamides (pharmacology)