title: Statin DecreasesHelicobacter pyloriBurden in Macrophages by Promoting Autophagy.
abstract: Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been found to provide protective effects against several bacterial infectious diseases. Although the use of statins has been shown to enhance antimicrobial treatedHelicobacter pylorieradication and reduceH. pylori-mediated inflammation, the mechanisms underlying these effects remain unclear. In this study,in vitroandex vivomacrophage models were established to investigate the molecular pathways involved in statin-mediated inhibition ofH.pylori-induced inflammation. Our study showed that statin treatment resulted in a dose-dependent decrease in intracellularH.pyloriburden in both RAW264.7 macrophage cells and murine peritoneal exudate macrophages (PEMs). Furthermore, statin yielded enhanced early endosome maturation and subsequent activation of the autophagy pathway, which promotes lysosomal fusion resulting in degradation of sequestered bacteria, and in turn attenuates interleukin (IL)-1β production. These results indicate that statin not only reduces cellular cholesterol but also decreases theH.pyloriburden in macrophages by promoting autophagy, consequently alleviatingH.pylori-induced inflammation.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical UniversityTaichung, Taiwan; Department of Pulmonary and Critical Care Medicine, China Medical University HospitalTaichung, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Liao
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical UniversityTaichung, Taiwan; Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan.
authors.forename: Mei-Zi
authors.initials: MZ
authors.lastname: Huang
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University Taichung, Taiwan.
authors.forename: Michelle Lily
authors.initials: ML
authors.lastname: Wang
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical UniversityTaichung, Taiwan; Department of Urology, University of Texas Southwestern Medical CenterDallas, TX, USA.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University Taichung, Taiwan.
authors.forename: Tzu-Li
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Fooyin University Kaohsiung, Taiwan.
authors.forename: Horng-Ren
authors.initials: HR
authors.lastname: Lo
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University Taichung, Taiwan.
authors.forename: Yi-Jiun
authors.initials: YJ
authors.lastname: Pan
authors.affiliation: Department of Laboratory Medicine, Chang Gung Memorial Hospital Taoyuan, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Sun
authors.affiliation: Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University Taoyuan, Taiwan.
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Kao
authors.affiliation: Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University Taoyuan, Taiwan.
authors.forename: Hui-Jing
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan; Graduate Institute of Basic Medical Science, School of Medicine, China Medical UniversityTaichung, Taiwan; Department of Nursing, Asia UniversityTaichung, Taiwan; Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Children's Hospital and Chang Gung Memorial HospitalTaoyuan, Taiwan.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D058491:Bacterial Load; D002478:Cells, Cultured; D016480:Helicobacter pylori / Q000276:immunology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology*; D051379:Mice
chemical_list: D000900:Anti-Bacterial Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: HMG-CoA reductase; Helicobacter pylori; autophagy; cholesterol; statin