1. Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy
André M. Cantin, Dominik Hartl, Michael W. Konstan, James F. Chmiel 
Journal of Cystic Fibrosis 
Volume 14, Issue 4, Pages (July 2015)
DOI: /j.jcf
Copyright © 2015 European Cystic Fibrosis Society. Terms and Conditions

2. Fig. 1
Illustrated are some of the potential links between CFTR deficiency and intense airway inflammation. The lack of functional CFTR leads to a loss of chloride and bicarbonate secretion into the airway surface fluid. Viscous mucin-rich material is tethered to the airway surface and clearance of bacteria is decreased. Low pH inhibits host anti-bacterial killing at the airway surface. CFTR deficiency is also associated with a low docosahexaenoic acid (DHA) to arachidonic acid ratio in cell membranes and favors TLR4-dependent inflammation (DAMPs: damage-associate molecular patterns). S100A8, A9 and A12 are neutrophil-derived inflammatory proteins. NFκB-dependent transcription is increased and Nrf2 signaling is blunted in CFTR-deficient cells. NFκB activation and defective Nrf2 signaling combine to increase neutrophil chemotaxis, decrease glutathione synthesis and increase mucin transcription and exocytosis. Neutrophil abundance and activation increase the release of proteases, oxidants and other toxic products that can inhibit CFTR, degrade airway tissues and induce bronchiectasis. Black lines with arrows represent induced pathways; red lines represent inhibition.
Journal of Cystic Fibrosis  , DOI: ( /j.jcf )
Copyright © 2015 European Cystic Fibrosis Society. Terms and Conditions