title: COX-2 expression and inflammatory effects by diesel exhaust particles in vitro and in vivo.
abstract: Recent studies have shown that diesel exhaust particles (DEP) have adverse effects on the respiratory tract in vitro and in vivo, related to various pro-inflammatory cytokines and inflammatory mediators. The inflammation induced by the production of cyclooxygenase (COX)-2, an important mediator of inflammation and tumor promotion, and excess eicosanoids may be central to the pathogenesis of DEP-induced airway inflammation. However, the role of COX-2 in the pathogenesis of DEP-induced lung inflammation remains unclear, especially in vivo. In this study, we demonstrated that treatment with 50 microg/ml of DEP for 24h induced the expression of the COX-2 gene at both the transcriptional and protein levels, which led to an increase in the release of prostaglandin E(2) (PGE(2)) in A549 cells. In addition, the increased levels of COX-2 and PGE(2) by DEP exposure were significantly suppressed by treatment with 50 pg/ml of dexamethasone (Dex). We also showed that exposure to 25 mg/kg of DEP induced the expression of the COX-2 protein in mouse lung tissues, and this increased COX-2 expression was attenuated by pretreatment with 5 mg/kg of Dex. These findings suggest that COX-2 may play an important role in the pathogenesis of DEP-induced pulmonary inflammation, which is effectively inhibited by glucocorticoid treatment.
authors.affiliation: Department of Occupational and Environmental Medicine, St. Mary's Hospital, The Catholic University of Korea, Seoul 150-713, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Ahn
authors.forename: Hyoung-Kyu
authors.initials: HK
authors.lastname: Yoon
authors.forename: Bo Keun
authors.initials: BK
authors.lastname: Jee
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Ko
authors.forename: Kweon-Haeng
authors.initials: KH
authors.lastname: Lee
authors.forename: Hyung Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Lim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D052638:Particulate Matter; D001335:Vehicle Emissions; D003907:Dexamethasone; D051546:Cyclooxygenase 2; D015232:Dinoprostone