Review Highlights Recent Research Advances in Cystic Fibrosis Airway Inflammation

In a special article published in the journal Mediators of Inflammation, a team of researchers led by Nades Palaniyar from the Lung Innate Immunity Research Laboratory at The Hospital for Sick Children Research Institute in Toronto, Canada reviewed the current research advances in the field of Cystic fibrosis (CF).

Cystic Fibrosis (CF) is a genetic disorder that affects mostly the lungs but also the pancreas, liver, kidneys and intestine. Long-term issues include difficulty breathing and coughing up sputum as a result of frequent lung infections.

CF is an autosomal recessive disorder. It is caused by the presence of mutations in both copies of the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR).  CFTR is involved in production of sweat, digestive fluids, and mucus. When CFTR is not functional, secretions which are usually thin instead become thick.

In recent years, there have been major advances in the treatment options for patients with CF. With novel CFTR-targeting therapies, there are now opportunities to correct CFTR dysfunction and improve pulmonary function in some patients.

However, airway inflammation remains a major factor in the management of the condition, and in the review tiled “New Developments in Cystic Fibrosis Airway Inflammation,” the authors focused on the current evidence regarding the role of airway inflammation in the development of chronic CF lung damage.

The regulatory mechanisms of CF airway inflammation remain poorly understood, but epithelial dysfunction seems to play a central role in the development of CF-specific inflammatory responses, with a recent study showing that ESE-1 may play a role in regulating CF airway inflammation via its effect on the expression of ICAM-1.

ESE-1 is induced in response to inflammatory cytokines and lipopolysaccharide in vascular smooth muscle cells, endothelial cells, and cells of the monocyte-macrophage lineage. ICAM-1 (Intercellular Adhesion Molecule 1) also known as CD54 (Cluster ofDifferentiation 54) is a protein that in humans is encoded by the ICAM-1 gene.

Another study has shown that phosphoinositide 3-kinases are involved in cellular regulatory functions including cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking.  In that study, phosphoinositide 3-kinase PI3Kγ was found to play a role in the regulation of neutrophilic inflammation in CF.

Another of the new developments in the field of CF is the discovery that nitric oxide deficiency in CF airways contributes to the increased risk of infections with pathogens such as Pseudomonas aeruginosa.

According to the authors, the role of ribonucleic acid (RNA) functions as a messenger in transcription but also that small noncoding RNA molecules (microRNA) plays important roles in post transcriptional regulation and modification, and is now being studied in the field of CF.

The authors concluded the review by hoping that it has stimulated interest for research ideas and therapeutic avenues in the field of CF.