title: Surfactant-associated protein B is critical to survival in nickel-induced injury in mice.
abstract: The etiology of acute lung injury is complex and associated with numerous, chemically diverse precipitating factors. During acute lung injury in mice, one key event is epithelial cell injury that leads to reduced surfactant biosynthesis. We have previously reported that transgenic mice that express transforming growth factor alpha (TGFA) in the lung were protected during nickel-induced lung injury. Here, we find that the mechanism by which TGFA imparts protection includes maintenance of surfactant-associated protein B (SFTPB) transcript levels and epidermal growth factor receptor-dependent signaling in distal pulmonary epithelial cells. This protection is complex and not accompanied by a diminution in inflammatory mediator transcripts or additional stimulation of antioxidant transcripts. In mouse lung epithelial (MLE-15) cells, microarray analysis demonstrated that nickel increased transcripts of genes enriched in MTF1, E2F-1, and AP-2 transcription factor-binding sites and decreased transcripts of genes enriched in AP-1-binding sites. Nickel also increased Jun transcript and DNA-binding activity, but decreased SFTPB transcript. Expression of SFTPB under the control of a doxycycline-sensitive promoter increased survival during nickel-induced injury as compared with control mice. Together, these findings support the idea that maintenance of SFTPB expression is critical to survival during acute lung injury.
authors.affiliation: Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219-3130, USA.
authors.forename: Kiflai
authors.initials: K
authors.lastname: Bein
authors.forename: Scott C
authors.initials: SC
authors.lastname: Wesselkamper
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Liu
authors.forename: Maggie
authors.initials: M
authors.lastname: Dietsch
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Majumder
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Concel
authors.forename: Mario
authors.initials: M
authors.lastname: Medvedovic
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Sartor
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Henning
authors.forename: Carmen
authors.initials: C
authors.lastname: Venditto
authors.forename: Michael T
authors.initials: MT
authors.lastname: Borchers
authors.forename: Aaron
authors.initials: A
authors.lastname: Barchowsky
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Weaver
authors.forename: Jay W
authors.initials: JW
authors.lastname: Tichelaar
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Prows
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Korfhagen
authors.forename: William D
authors.initials: WD
authors.lastname: Hardie
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Bachurski
authors.forename: George D
authors.initials: GD
authors.lastname: Leikauf
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced*; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009532:Nickel / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology; D015996:Survival Rate; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000336:Aerosols; D016755:Proto-Oncogene Proteins c-jun; D037701:Pulmonary Surfactant-Associated Protein B; D018808:Transcription Factor AP-1; D016211:Transforming Growth Factor alpha; D009532:Nickel