title: 1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) attenuates airway remodeling in a murine model of chronic asthma.
abstract: OBJECTIVE
  1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) has immune- and inflammation-modulating properties in asthma, but its possible effects on asthmatic airway remodeling remain uncertain. In this study, we investigated the effects of 1,25-(OH)(2)D(3) on airway remodeling in a murine model of chronic asthma and investigated its role in regulating nuclear factor-κB (NF-κB) activation.
  
  
  METHODS
  BALB/c mice were sensitized to ovalbumin (OVA) and subsequently exposed to intranasal OVA challenges for 9 weeks. Some mice also received an intraperitoneal injection of 1,25-(OH)(2)D(3) at the time of challenge. At the end of the challenge period, mice were evaluated for chronic airway inflammation and airway remodeling. Nuclear translocation of NF-κB p65 in lung tissue was examined by Western blot. Inhibitor of NF-κB alpha (IκBα) expression was determined by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot. Phosphorylated IκBα protein expression was also determined by Western blot.
  
  
  RESULTS
  1,25-(OH)(2)D(3) treatment reduced OVA-induced chronic inflammation in lung tissue and attenuated established structural changes of the airways, including subepithelial collagen deposition, goblet cell hyperplasia, and increased airway smooth muscle mass. 1,25-(OH)(2)D(3) also inhibited the nuclear translocation of NF-κB p65 in lung tissue. Concurrently, 1,25-(OH)(2)D(3) induced increased IκBα protein levels via inducing increased IκBα mRNA levels and decreased IκBα phosphorylation.
  
  
  CONCLUSIONS
  1,25-(OH)(2)D(3) could attenuate asthmatic airway remodeling and its inhibition of NF-κB activation may underlie this protective effect.
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Lai
authors.forename: Changgui
authors.initials: C
authors.lastname: Wu
authors.forename: Jingfang
authors.initials: J
authors.lastname: Hong
authors.forename: Yingfang
authors.initials: Y
authors.lastname: Song
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D020672:I-kappa B Proteins / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D010047:Ovalbumin; D002117:Calcitriol