ABCMdb

PMID: 19700644

Nichols DP, Ziady AG, Shank SL, Eastman JF, Davis PB
The triterpenoid CDDO limits inflammation in preclinical models of cystic fibrosis lung disease.
Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L828-36. Epub 2009 Aug 21., [PubMed]

Sentences

No. Mutations Sentence Comment

10 ABCC7 p.Arg117His In our experiments, mice carrying the R117H Cftr mutation have significantly reduced airway inflammatory responses to both LPS and flagellin when treated with CDDO before inflammatory challenge. Login to comment 42 ABCC7 p.Arg117His In this paper, we test the hypothesis that the synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) can effectively suppress the inflammatory response in preclinical models of CF airway inflammation using human airway epithelial cells lacking CFTR and mice carrying the Cftr mutation R117H. Login to comment 119 ABCC7 p.Arg117His Thirty-two mice with the R117H CFTR mutation (B6.129S6-Cftrtm2Mrc ) and 18 wild-type (WT) mice on the C57BL/6 genetic background were bred and housed in our Animal Research Core facility under specific pathogen-free conditions. Login to comment 120 ABCC7 p.Arg117His R117H mice were selected as this is a human CF mutation and may avoid additional NF-␬B activation caused by protein misfolding and the buildup of dysfunctional proteins in the endoplasmic reticulum (ER) that can occur with other mutations (e.g., ⌬F508) (45). Login to comment 122 ABCC7 p.Arg117His ABCC7 p.Ser489* Electrophysiological phenotype (i.e., nasal potential difference) and inflammatory responses in the lung to P. aeruginosa are very similar in R117H mice and multiple other CF transgenic mice, including mice bearing the ⌬F508 or S489X mutation (40). Login to comment 254 ABCC7 p.Arg117His In addition to characterizing the effect of CDDO in CF models, a primary aim of this research was to test the biological relevance of this synthetic triterpenoid in an in vivo CF model using mice carrying the R117H Cftr mutation. Login to comment