ABCMdb

PMID: 22825912

Gavina M, Luciani A, Villella VR, Esposito S, Ferrari E, Bressani I, Casale A, Bruscia EM, Maiuri L, Raia V
Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice.
Pediatr Pulmonol. 2012 Jul 23. doi: 10.1002/ppul.22637., [PubMed]

Sentences

No. Mutations Sentence Comment

20 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ß 2012 Wiley Periodicals, Inc. (P. aeruginosa) endobronchial infection, is the leading cause of morbidity and mortality and much efforts are employed to improve the efficacy of therapeutic regimens to preserve lung function in CF patients.1,2 Treatment advances over the past several decades have raised the median predicted survival age from less than 5 years in the 1940s to over 37 years old today.3 Since identification of CFTR gene in 19893 new therapeutic strategies, as gene therapy, have been proposed and, more recently, CFTR-repairing therapies aimed at correcting the basic defect of CFTR protein.4 Several novel compounds emerged as promising tools for treating CF patients and a newly identified potentiator of CFTR channel activity, VX-770, proved its efficacy in improving lung function of the small subset of CF patients that carry G551D CFTR mutant.5 However, G551D CFTR mutation is very rare in most CF popula- tions6,7 and the efficacy of the CFTR-repairing therapy on the most common CFTR mutations, as F508del-CFTR, is far to be proved.4,5 Clinical studies combining corrector and potentiator molecules have to be awaited to evaluate their clinical benefit.4,5 Awaiting more effective therapies that can target specific defects in the CFTR gene, most candidate drugs are being tested to treat CF symptoms. Login to comment 113 ABCC7 p.Trp1282* HA Controls Oxidative Stress and TG2 Activation in CF Epithelia Lung inflammation with increased levels of reactive oxygen species (ROS) characterizes CF airway epithelia as a consequence of defective CFTR function.29 We have reported that a complex alteration of redox balance drives a sequential cascade of events involving upregulation of TG2, autophagy inhibition and lung inflammation in human and mouse CF airways.29-31 To unravel whether the effects of exogenous HA in damping down lung inflammation in vivo was linked to the ability to control the ROS-mediated events, we cultured airway epithelial IB3-1 and CFBE41o cells, carrying DF508/W1282X or DF508/DF508 CFTR mutations respectively,29-31 below referred as ''CF cells,`` with or without 100 mg/ml HA for 24 hr in presence or absence of PA-LPS stimulation (1 mg/ml). Login to comment