Abstract
ObjectiveTo explore the effects of atorvastatin on expression of cyclooxygenase-2 (COX-2) in human pulmonary epithelial cells (A549).MethodsA549 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.ResultsLPS 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).ConclusionAtorvastatin down-regulates LPS-induced expression of the COX-2 and consequently inhibits production of PGE2 in cultured A549 cells.
Highlights
Human pulmonary epithelial cell is one of major sources of productive inflammatory biomediators, such as prostaglandin E2 (PGE2), interleukin-6 (IL-6), in respiratory inflammatory diseases [1]
Cyclooxygenase-2 (COX-2) is an inducible enzyme that is expressed in response to inflammatory cytokines, and it is responsible for the synthesis of pro-inflammatory PGs such as PGE2
3.1 Dose- and time-dependent effects of LPS on COX-2 mRNA expression and PGE2 production To determine the concentration dependent effect of LPS, A549 cells were incubated with various concentrations of LPS for 9 h
Summary
Human pulmonary epithelial cell is one of major sources of productive inflammatory biomediators, such as prostaglandin E2 (PGE2), interleukin-6 (IL-6), in respiratory inflammatory diseases [1]. Increased expression of COX-2 and production of PGE2 have been found in pulmonary inflammatory disorders [2]. Atorvastatin reduces expression of the COX2 in cultured vascular smooth muscle cells [4]. It is not clear whether Atorvastatin affects COX-2 expression in human pulmonary epithelial cells. Because of importance of COX-2 in inflammatory respiratory diseases, we tested the effects of Atorvastatin on lipopolysaccharide (LPS)-induced expression of COX-2 in cultured human pulmonary epithelial cells
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