Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants

Rae, C. , Cherry, J.I., Land, F.M. and Land, S.C. (2006) Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants. Biochemical and Biophysical Research Communications, 349(1), pp. 416-425. (doi: 10.1016/j.bbrc.2006.08.067)

Abstract

Inflammation induces premature maturation of the fetal lung but the signals causing this effect remain unclear. We determined if nitric oxide (NO) synthesis, evoked by Escherichia coli lipopolysaccharide (LPS, 2 μg ml−1), participated in this process. Fetal rat lung airway surface complexity rose 2.5-fold over 96 h in response to LPS and was associated with increased iNOS protein expression and activity. iNOS inhibition by N6-(1-iminoethyl)-l-lysine-2HCl (L-NIL) abolished this and induced airway atrophy similar to untreated explants. Surfactant protein-C (SP-C) expression was also induced by LPS and abolished by L-NIL. As TGFβ suppresses iNOS activity, we determined if feedback regulation modulated NO-dependent maturation. LPS induced TGFβ1 release and SMAD4 nuclear translocation 96 h after treatment. Treatment of explants with a blocking antibody against TGFβ1 sustained NO production and airway morphogenesis whereas recombinant TGFβ1 antagonized these effects. Feedback regulation of NO synthesis by TGFβ may, thus, modulate airway branching and maturation of the fetal lung.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rae, Dr Colin
• Authors: Rae, C., Cherry, J.I., Land, F.M., and Land, S.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Biochemical and Biophysical Research Communications
• ISSN: 0006-291X
• Published Online: 22 August 2006