Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema
| Autor: | Sang Do Lee, Gu Seob Roh, Byeong Tak Jeon, Yu Ji Cho, Irina Tsoy Nizamudtinova, Ji Hyun Lee, Jin Won Huh, Jong Deog Lee, Young Sil Hwang, Jin Hyun Kim, Yeon-Mok Oh, Hye Jung Kim, Chin-ok Yi |
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| Rok vydání: | 2010 |
| Předmět: |
Male
musculoskeletal diseases Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Physiology medicine.drug_class Anti-Inflammatory Agents Antigens Differentiation Myelomonocytic Nitric Oxide Synthase Type II Nitric Oxide Dinoprostone Anti-inflammatory Tobacco smoke Cell Line Rats Sprague-Dawley Mice NF-KappaB Inhibitor alpha Antigens CD Physiology (medical) medicine Animals Phosphorylation Respiratory system Inflammation Smoke Sulfonamides Lung Cyclooxygenase 2 Inhibitors business.industry Macrophages Smoking Respiratory disease NF-kappa B Cell Biology medicine.disease Rats Pulmonary Alveoli medicine.anatomical_structure Pulmonary Emphysema Celecoxib Cyclooxygenase 2 Lung disease Pyrazoles I-kappa B Proteins lipids (amino acids peptides and proteins) business medicine.drug |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 299:L184-L191 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | 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 PGE2production 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-IκBα and NF-κB in CS-treated rat lung. In addition, there was an inhibitory effect of celecoxib on the COX-2 expression and NF-κB activation in LPS-stimulated RAW 264.7 macrophages. Celecoxib also attenuated NF-κB 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-κB-regulated gene expression, which ultimately reduces the progression of CS-induced pulmonary emphysema. |
| Databáze: | OpenAIRE |
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