Endothelin-1 increases expression of cyclooxygenase-2 and production of interlukin-8 in hunan pulmonary epithelial cells.
Inducible cyclooxygenase (COX-2) and inflammatory cytokines play important roles in inflammatory processes of chronic obstructive pulmonary disease (COPD). Endothelin-1 (ET-1) might be also involved in the pathophysilogical processes in COPD. In the present study, we determined whether ET-1 could regulate the expression of COX-2 and alter the production of interleukin-8 (IL-8) in human pulmonary epithelial cells (A549). Induced sputum samples were collected from 13 stable COPD patients and 14 healthy subjects. The COX-2 protein, ET-1, PGE(2) and IL-8 in these sputum samples were analyzed. A549 cells were incubated with ET-1 in the presence or absence of celecoxib, a selective COX-2 inhibitor. The expression of COX-2 protein in the cell and the amounts of PGE(2) and IL-8 in the medium were measured. The levels of COX-2 protein, ET-1, PGE(2) and IL-8 were significantly increased in induced sputum from COPD patients when compared to healthy subjects. ET-1 increased the expression of COX-2 protein, as well as the production of PGE(2) in A549 cells. Increased production of PGE(2) was inhibited by celecoxib. ET-1 also increased the production of IL-8. Interestingly, ET-1-induced production of IL-8 was also inhibited by celecoxib. These findings indicate that ET-1 plays important roles in regulating COX-2 expression and production of IL-8 in A549 cells. ET-1 mediated production of IL-8 is likely through a COX-2-dependent mechanism.
Peng
Hong
H
Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Chen
Ping
P
Cai
Ying
Y
Chen
Yan
Y
Wu
Qing-Hua
QH
Li
Yun
Y
Zhou
Rui
R
Fang
Xiang
X
D000368:Aged; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D013183:Sputum / Q000378:metabolism
D019332:Endothelin-1; D016209:Interleukin-8; D051546:Cyclooxygenase 2; D015232:Dinoprostone