Atorvastatin reduces lipopolysaccharide-induced expression of cyclooxygenase-2 in human pulmonary epithelial cells.
OBJECTIVE
To explore the effects of atorvastatin on expression of cyclooxygenase-2 (COX-2) in human pulmonary epithelial cells (A549).


METHODS
A549 cells were incubated in DMEM medium containing lipopolysaccharide (LPS) in the presence or absence of atorvastatin. After incubation, the medium was collected and the amount of prostaglandin E2 (PGE2) was measured by enzyme-linked immunosorbent assay (ELISA). The cells were harvested, and COX-2 mRNA and protein were analyzed by RT-PCR and western-blot respectively.


RESULTS
LPS increased the expression of COX-2 mRNA and production of PGE2 in a dose- and time-dependent manner in A549. Induction of COX-2 mRNA and protein by LPS were inhibited by atorvastatin in a dose-dependent manner. Atorvastatin also significantly decreased LPS-induced production of PGE2. There was a positive correlation between reduced of COX-2 mRNA and decreased of PGE2 (r = 0.947, P < 0.05).


CONCLUSIONS
Atorvastatin down-regulates LPS-induced expression of the COX-2 and consequently inhibits production of PGE2 in cultured A549 cells.
Wu
ShangJie
S
Division of Cardiovascular Disease, Department of Internal Medicine, The Second Xiangya Hospital, Center Southern University, Changsha, Hunan, China. wu_shangjie@hotmail.com
Duan
Shu
S
Zhao
ShuiPing
S
Cai
Ying
Y
Chen
Ping
P
Fang
Xiang
X
D000069059:Atorvastatin; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D011758:Pyrroles / Q000008:administration & dosage; D020545:Respiratory Mucosa / Q000187:drug effects / Q000201:enzymology*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011758:Pyrroles; D000069059:Atorvastatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone