title: Lipopolysaccharide induced connective tissue growth factor gene expression in human bronchial epithelial cells.
abstract: OBJECTIVE
  Connective tissue growth factor (CTGF) is up-regulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke and repeated bacterial infections, both of which are rich sources of LPS, are major causes of COPD. The high levels of LPS in lung epithelial lining fluid also suggest that it may have a considerable impact on the airway epithelium, in terms of cytokine and growth factor production. The aim of this study was to clarify the mechanism of LPS-induced CTGF expression in bronchial epithelial cells.
  
  
  METHODS
  The expression and transcriptional regulation of the CTGF gene were assessed using the cultured human bronchial epithelial cell line, BEAS-2B.
  
  
  RESULTS
  LPS significantly up-regulated CTGF mRNA expression in a dose-dependent fashion, with 100 microg/mL LPS causing a twofold increase after 2 h. CTGF protein expression was also up-regulated by LPS after 8 h. Transforming growth factor-beta1 mRNA expression was not changed by LPS treatment. A pharmacological inhibitor of nuclear factor (NF)-kappaB, MG132, inhibited LPS-induced CTGF mRNA expression. Furthermore, luciferase assays demonstrated that deletion of base pairs -253 to -53 from the CTGF promoter, where the Smad and proximal NF-kappaB binding sites are located, decreased the induction of CTGF by LPS. After stimulation with LPS, the p65 subunit of NF-kappaB was shown to be bound to the CTGF promoter in vitro and in situ.
  
  
  CONCLUSIONS
  LPS directly induced CTGF expression in bronchial epithelial cells, independently of transforming growth factor-beta1, suggesting a possible mechanism for airway remodelling in COPD that is induced by smoking and repeated bacterial infections.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Nishioka
authors.forename: Emiko
authors.initials: E
authors.lastname: Ogawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kinose
authors.forename: Akane
authors.initials: A
authors.lastname: Haruna
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ohara
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.forename: Yuma
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ito
authors.forename: Hisako
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mio
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chin
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Hirai
authors.forename: Shigeo
authors.initials: S
authors.lastname: Muro
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D001980:Bronchi / Q000378:metabolism*; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007976:Leupeptins / Q000008:administration & dosage / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D007976:Leupeptins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D055513:Connective Tissue Growth Factor; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde