title: 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.affiliation: Departments of Anatomy, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, South Korea.
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Chin-ok
authors.initials: CO
authors.lastname: Yi
authors.forename: Yu Ji
authors.initials: YJ
authors.lastname: Cho
authors.forename: Byeong Tak
authors.initials: BT
authors.lastname: Jeon
authors.forename: Irina Tsoy
authors.initials: IT
authors.lastname: Nizamudtinova
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Yeon-Mok
authors.initials: YM
authors.lastname: Oh
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Huh
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Young Sil
authors.initials: YS
authors.lastname: Hwang
authors.forename: Sang Do
authors.initials: SD
authors.lastname: Lee
authors.forename: Jong Deog
authors.initials: JD
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000068579:Celecoxib; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011650:Pulmonary Alveoli / Q000473:pathology; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects*; D013449:Sulfonamides / Q000494:pharmacology*; D000097382:CD68 Molecule
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D015232:Dinoprostone; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011720:Pyrazoles; D013449:Sulfonamides; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; C496318:Nos2 protein, rat