Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease.
Date Issued
2024-07-01
Date Acceptance
2024-07-09
Citation
European Respiratory Review, 2024, 33 (173)
ISSN
0905-9180
Publisher
European Respiratory Society
Journal / Book Title
European Respiratory Review
Volume
33
Issue
173
Copyright Statement
©The authors 2024 This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39293854
PII: 33/173/240001
Subjects
AIRWAY INFLAMMATION
CATALYTIC-ACTIVITY
CATHEPSIN-G ACTIVITY
CELL-SURFACE
ELASTASE
GENE-EXPRESSION
Life Sciences & Biomedicine
LUNG-FUNCTION DECLINE
MATRIX METALLOPROTEINASES
Respiratory System
Science & Technology
SPUTUM BIOMARKERS
TRANSMEMBRANE CONDUCTANCE REGULATOR
Publication Status
Published
Coverage Spatial
England
Article Number
240001
Date Publish Online
2024-09-18