Universität zu Köln

Thomassen, Jan C., Trojan, Tobias, Walz, Maxine, Vohlen, Christina, Fink, Gregor, Rietschel, Ernst, Alcazar, Miguel A. Alejandre and Van Koningsbruggen-Rietschel, Silke (2021). Reduced neutrophil elastase inhibitor elafin and elevated transforming growth factor-beta(1) are linked to inflammatory response in sputum of cystic fibrosis patients with Pseudomonas aeruginosa. ERJ Open Res., 7 (3). SHEFFIELD: EUROPEAN RESPIRATORY SOC JOURNALS LTD. ISSN 2312-0541

Full text not available from this repository.

Abstract

Research question Pulmonary disease progression in patients with cystic fibrosis (CF) is characterised by inflammation and fibrosis and aggravated by Pseudomonas aeruginosa (Pa). We investigated the impact of Pa specifically on: 1) protease/antiprotease balance; 2) inflammation; and 3) the link of both parameters to clinical parameters of CF patients. Methods Transforming growth factor-beta(1) (TGF-beta(1)), interleukin (IL)-1 beta, IL-8, neutrophil elastase (NE) and elastase inhibitor elafin were measured (ELISA assays), and gene expression of the NF-kappa B pathway was assessed (reverse transcriptase PCR) in the sputum of 60 CF patients with a minimum age of 5 years. Spirometry was assessed according to American Thoracic Society guidelines. Results Our results demonstrated the following: 1) NE was markedly increased in Pa-positive sputum, whereas elafin was significantly decreased; 2) increased IL-1 beta/IL-8 levels were associated with both Pa infection and reduced forced expiratory volume in 1 s, and sputum TGF-beta(1) was elevated in Pa-infected CF patients and linked to an impaired lung function; and 3) gene expression of NF-kappa B signalling components was increased in sputum of Pa-infected patients, and these findings were positively correlated with IL-8. Conclusion Our study links Pa infection to an imbalance of NE and NE inhibitor elafin and increased inflammatory mediators. Moreover, our data demonstrate an association between high TGF-beta(1) sputum levels and a progress in chronic lung inflammation and pulmonary fibrosis in CF. Controlling the excessive airway inflammation by inhibition of NE and TGF-beta(1) might be promising therapeutic strategies in future CF therapy and a possible complement to cystic fibrosis transmembrane conductance regulator (CFTR) modulators.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thomassen, Jan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Trojan, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Walz, Maxine UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gregor UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, Ernst UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel A. Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Koningsbruggen-Rietschel, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-564873
DOI:	10.1183/23120541.00636-2020
Journal or Publication Title:	ERJ Open Res.
Volume:	7
Number:	3
Date:	2021
Publisher:	EUROPEAN RESPIRATORY SOC JOURNALS LTD
Place of Publication:	SHEFFIELD
ISSN:	2312-0541
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; YOUNG-CHILDREN; RISK-FACTORS; INFECTION; PATHOPHYSIOLOGY; BRONCHIECTASIS; INDIVIDUALS; BIOMARKERS; DECLINE; DISEASE Multiple languages Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56487