Early inflammation in the airways of a cystic fibrosis foetus

Abstract

In cystic fibrosis patients, inflammation is often considered to be secondary to chronic infections. In the present study, we show increased levels of pro-inflammatory proteins in the lungs of a cystic fibrosis foetus compared to the lungs of two normal foetuses. Our findings suggest therefore the existence of an early intrinsic pro-inflammatory state in cystic fibrosis airways.

Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

“…It was generally considered that the abnormal mucus favors infections and lung colonization by bacteria, which in turn leads to a chronic inflammation and subsequent angiogenesis [14,15]. However, several recent findings from our and other groups suggest that some degree of inflammation could be observed in CF cells or lungs even before any infection [16][17][18][19]. Our results newly show that human epithelial fetal tracheal cells carrying the homozygous CFTR mutation DF508 display a pro-angiogenic state compared to control epithelial cells.…”

“…Although there is still a debate about a pre-existing proinflammatory state in CF epithelial cells, our group and others have demonstrated constitutive activation of two important transcription factors that play central role in the onset and persistence of an inflammatory process: NF-jB and AP-1 [16,[22][23][24][25][26]. Furthermore, we have shown a role for the ERK1/2 signaling pathway in pro-inflammatory gene expression in CF cells (see Footnote qq).…”

Ceramide and sphingosine in pulmonary infections

“…More than 80% of adult cystic fibrosis patients are infected with P. aeruginosa. Furthermore, cystic fibrosis airways are characterized by chronic inflammation with an imbalance between proinflammatory and antiinflammatory cytokines (Inoue et al, 1994;Bonfield et al, 1995;Khan et al, 1995;Tirouvanziam et al, 2000;Venkatakrishnan et al, 2000;Tabary et al, 2001;Oceandy et al, 2002;Verhaeghe et al, 2007). An increase in the concentrations of inflammatory mediators was observed in lungs from aborted fetuses, a finding suggesting that aseptic inflammation occurs very early in cystic fibrosis.…”

The National Consensus Project* «cystic Fibrosis: Definition, Diagnostic Criteria, and Therapy». Section «inhalation Therapy» (Abridged)

“…В ответ на воспале-ние стенки бронхов утолщаются, в них увеличивает-ся число гладкомышечных клеток, причем в большей степени это выражено в периферических дыхательных путях [6]. Респираторная аллергия у больных МВ встре-чается в 48-60% случаев [6], а бронхиальная астма -у 1/3 больных [7].…”