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

Bein K,Wesselkamper SC,Liu X,Dietsch M,Majumder N,Concel VJ,Medvedovic M,Sartor MA,Henning LN,Venditto C,Borchers MT,Barchowsky A,Weaver TE,Tichelaar JW,Prows DR,Korfhagen TR,Hardie WD,Bachurski CJ,Leikauf GD

doi

10.1165/rcmb.2008-0317OC

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

226-36

issue

2

eissn

1044-1549

issn

1535-4989

pii

2008-0317OC

journal_volume

41

pub_type

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