title: Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells.
abstract: Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.
authors.affiliation: Internal Medicine II, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Iwata
authors.forename: R
authors.initials: R
authors.lastname: Shirai
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Kushima
authors.forename: S
authors.initials: S
authors.lastname: Otani
authors.forename: K
authors.initials: K
authors.lastname: Hashinaga
authors.forename: K
authors.initials: K
authors.lastname: Umeki
authors.forename: K
authors.initials: K
authors.lastname: Kishi
authors.forename: I
authors.initials: I
authors.lastname: Tokimatsu
authors.forename: K
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: J
authors.initials: J
authors.lastname: Kadota
mesh_terms: D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008798:Mevalonic Acid / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D020742:rhoA GTP-Binding Protein; D017035:Pravastatin; D008798:Mevalonic Acid