title: Krüppel-like factor 5 mediates proinflammatory cytokine expression in lipopolysaccharide-induced acute lung injury through upregulation of nuclear factor-κB phosphorylation in vitro and in vivo.
abstract: Acute lung injury (ALI) is associated with an inflammation-mediated process, and the transcription factor, Krüppel-like factor 5 (KLF5), might play a crucial role in inflammatory lung disease. In this study, we evaluated KLF5, reactive oxygen species (ROS), and inflammatory responses in a lipopolysaccharide- (LPS-) induced ALI model to elucidate the role of KLF5 in ALI. Our data indicated that LPS upregulates proinflammatory cytokine expression in human bronchial epithelial cells in a dose-dependent manner. We observed upregulated KLF5 protein expression in human bronchial epithelial cells exposed to LPS, with peak expression 1 h after LPS treatment, and subsequent upregulation of p65 protein expression and p65 phosphorylation at Ser276. These results indicate that KLF5 mediates proinflammatory cytokine expression by upregulating nuclear factor-kappaB (NF-κB) phosphorylation at p65 in response to LPS. LPS treatment also increased ROS production and simultaneously upregulated KLF5 expression and NF-κB translocation. N-acetylcysteine significantly reduced ROS levels and KLF5 and NF-κB translocation in nuclear extracts. Therefore, N-acetylcysteine pretreatment before LPS exposure reduces ROS, downregulates KLF5 expression, and subsequently reduces inflammatory responses by scavenging ROS. Overall, our study results indicate that KLF5 mediates proinflammatory cytokine expression through upregulation of NF-κB phosphorylation at p65 in LPS-induced ALI.
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Hsiu-Lin
authors.identifier: 0000-0002-0565-4631
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Translational Research Center, Department of Medical Research, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Internal Medicine, Department of Chest Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Inn-Wen
authors.identifier: 0000-0001-8328-8684
authors.initials: IW
authors.lastname: Chong
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Translational Research Center, Department of Medical Research, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Internal Medicine, Department of Chest Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Jong-Rung
authors.initials: JR
authors.lastname: Tsai
authors.affiliation: Translational Research Center, Department of Medical Research, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
authors.affiliation: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Hui-Min
authors.identifier: 0000-0002-5162-9752
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Liu
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Translational Research Center, Department of Medical Research, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Po-Len
authors.initials: PL
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C492214:KLF5 protein, human; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species