COX-2 expression and inflammatory effects by diesel exhaust particles in vitro and in vivo.
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.
Ahn
Eun-Kyung
EK
Department of Occupational and Environmental Medicine, St. Mary's Hospital, The Catholic University of Korea, Seoul 150-713, Republic of Korea.
Yoon
Hyoung-Kyu
HK
Jee
Bo Keun
BK
Ko
Hye-Jin
HJ
Lee
Kweon-Haeng
KH
Kim
Hyung Jung
HJ
Lim
Young
Y
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*
D000893:Anti-Inflammatory Agents; D052638:Particulate Matter; D001335:Vehicle Emissions; D003907:Dexamethasone; D051546:Cyclooxygenase 2; D015232:Dinoprostone