title: Effect of pravastatin on bleomycin-induced acute lung injury and pulmonary fibrosis.
abstract: 1. Pravastatin is best known for its antilipidemic action. Recent studies have shown that statins have immunomodulatory and anti-inflammatory effects. The present study aimed to determine whether or not pravastatin can attenuate acute lung injury and fibrosis in a mouse model. 2. Bleomycin was given to C57BL6 mice through intratracheal instillation. Pravastatin was given through intraperitoneal injection. To study the effect of pravastatin on the early inflammatory phase and the late fibrotic phase, mice were killed on days 3, 7, 14 and 21. 3. Pravastatin attenuated the histopathological change of bleomycin-induced lung injury and fibrosis. The accumulation of neutrophils and increased production of tumor necrosis factor-α in bronchoalveolar lavage fluid were inhibited in the early inflammatory phase. Pravastatin effectively inhibited the increase of lung hydroxyproline content induced by bleomycin. Furthermore, pravastatin reduced the increased expression of transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), RhoA and cyclin D1. The increased levels of TGF-β1 and CTGF mRNA expression were also significantly inhibited by pravastatin. 4. Pravastatin effectively attenuated bleomycin-induced lung injury and pulmonary fibrosis in mice. Our results provide evidence for the therapeutic potential of pravastatin in the treatment of acute lung injury and pulmonary fibrosis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Chin Kook
authors.initials: CK
authors.lastname: Rhee
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Kim
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Kim
authors.forename: Sang Haak
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyung Kyu
authors.initials: HK
authors.lastname: Yoon
authors.forename: Seok Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Sook Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Soon Suk
authors.initials: SS
authors.lastname: Kwon
authors.forename: Kwan Hyung
authors.initials: KH
authors.lastname: Kim
authors.forename: Young Kyoon
authors.initials: YK
authors.lastname: Kim
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000633:toxicity*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012128:Respiratory Distress Syndrome / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D020742:rhoA GTP-Binding Protein
chemical_list: D000893:Anti-Inflammatory Agents; C526318:CCN2 protein, mouse; C530105:Ccnd1 protein, mouse; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D019938:Cyclin D1; D055513:Connective Tissue Growth Factor; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D017035:Pravastatin; D006909:Hydroxyproline