Premium
Post‐treatment with the heat shock protein 90 (hsp90) inhibitor, 17‐AAG, reduces pulmonary inflammation, hyper‐permeability and airway dysfunction associated with LPS‐induced acute lung injury (ALI) in mice.
Author(s) -
Dimitropoulou Christiana,
Joshi Atul,
Barabutis Nektarios,
Shaw Mary,
Patel Vijay,
Catravas John D
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1131.6
Subject(s) - bronchoalveolar lavage , evans blue , extravasation , heat shock protein , lung , vascular permeability , inflammation , pharmacology , medicine , hsp70 , chemistry , immunology , biochemistry , gene
Pre‐treatment with the heat shock protein 90 (hsp90) inhibitor, 17‐ AAG, reduces the magnitude of LPS‐induced ALI in mice. We now tested the hypothesis that post‐treatment with 17‐AAG would also reduce the magnitude of LPS‐induced ALI. 24h after the intratracheal instillation of vehicle or LPS (1.5mg/kg), mice received either vehicle or 17‐AAG (i.p. 10mg/kg). 48h later bronchoalveolar lavage fluid (BALF) was collected, and the number of cells and protein concentration were estimated as indicators of inflammation and permeability, respectively. In separate groups, lung capillary permeability was estimated by the Evans’ Blue Dye (EBD) method. LPS alone increased BALF cellularity (452±50 ×10 3 cells/ml vs 33±2 ×10 3 cells/ml in vehicle) and BALF protein concentration (204±5% from vehicle). 17‐AAG post‐treatment reduced the LPS‐induced BALF cellularity (140±32 ×10 3 cells/ml) and protein concentration (119±18% from vehicle). Furthermore, LPS produced a 193±18% increase in EBD extravasation which was also significantly reduced to 135±27% in mice post‐treated with 17‐AAG. In additional mice, pulmonary function tests were performed. LPS caused a nearly 100% increase in airway resistance that was completely prevented by post‐treatment with 17‐AAG. These data strongly suggest important reparative actions of hsp90 inhibitors when administered after the LPS insult.