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Effect of IL-6, IL-8 and glucocorticoids on the internalization of Pseudomonas aeruginosa (ATCC 27853) in cystic fibrosis bronchial epithelial cells
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0003-4946-3228
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
3Stockholm CF-centre, Department of Pediatrics, Karolinska University Hospital, Huddinge, Stockholm.
Örebro University, School of Medicine, Örebro University, Sweden.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Pseudomonas aeruginosa infection is common in cystic fibrosis (CF). Uptake of P. aeruginosa by the cell and the subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. CF airways have elevated levels of IL-6 and IL-8. Glucocorticoids (GCs) are anti-inflammatory but their use in CF is controversial. We studied the effect of IL- 6, IL-8 and GCs on bacterial internalization, apoptosis, and intracellular Ca2+concentration in CF bronchial epithelial (CFBE) cells and found that increased levels of IL-6 and IL-8 can increase the susceptibility of P. aeruginosa infected cells to apoptosis and/or internalization of these bacteria in CF cells. GCs decreased the extent of apoptosis in CFBE cells infected with P. aeruginosa, but may improve airway hydration by increasing the intracellular Ca2+ concentration. None of the GCs and cytokines affected apoptosis in cells not exposed to Pseudomonas. We conclude that increased levels of IL-6 and IL-8 may have important roles in the pathology of P. aeruginosa infection in CF airways. If internalization is beneficial for the host then GCs are not beneficial for the treatment of CF patients. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out. 

Keyword [en]
cystic fibrosis, Pseudomonas aeruginosa, internalization, apoptosis, glucocorticoids.
National Category
Pharmacology and Toxicology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-35865OAI: oai:DiVA.org:oru-35865DiVA: diva2:736255
Available from: 2014-08-05 Created: 2014-08-05 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Cell responses in infected and cystic fibrosis respiratory epithelium
Open this publication in new window or tab >>Cell responses in infected and cystic fibrosis respiratory epithelium
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Respiratory Epithelium. Örebro Studies in Medicine 99. Cystic fibrosis (CF) is caused by a mutation in a cAMP-activated chloride (Cl-) channel (CFTR). Mortality and morbidity in CF is mainly due to the deregulated responses of the airway epithelial cells. The purpose of the thesis was to investigate the behaviour of the airway epithelial cells that are involved in maintaining the homeostasis in the airways.

Nasal brush biopsies obtained from anesthetized human nasal mucosa can be an easy source to establish primary epithelial cell lines (Paper I). We found that CF and non CF cellular models cannot fully show the relation between CFTR and the phenotypic differences between CF and healthy cells (Paper II). The possibility to correct the Cl- transport defect in CF by the use of stable NOdonors, and ambroxol was investigated. NO-donors stimulated Cl- efflux, and decreased ENaC mRNA expression in CFBE cells (Paper III), while ambroxol increased Cl- efflux from CFBE cells, and showed a positive effect on the biosynthesis of CFTR (Paper IV). This suggests that these substances may be a potentially interesting group of compounds for the treatment of CF. Increased levels of IL-6 and IL-8 upon infection in CF cells can increase the susceptibility of P. aeruginosa infected CF cells to apoptosis and/or internalization of these bacteria in CF cells and hence, may have important roles in the pathology of P. aeruginosa infection in CF airways. If internalization is beneficial for the host then glucocorticoids (GCs) are not beneficial for the treatment of CF patients. However, GCs may improve airway hydration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out (Paper V). The neonatal isolates S. epidermidis 94B080 and S. aureus 90B083 can modulate CFTR and ENaC expression in airway epithelial cells, which may disturb the ion transport in the respiratory epithelium upon bacterial exposure. Airway epithelial cells also show excessive inflammatory responses to these bacteria, which means that these bacteria may induce pulmonary inflammation (Paper VI).

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2014. 85 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 99
Keyword
airway epithelial cells, cystic fibrosis, bacterial infection, CFTR, ENaC, chloride transport, intracellular calcium, P. aeruginosa internalization
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-32191 (URN)978-91-7668-984-4 (ISBN)
Public defence
2014-01-17, Bohmansalen, B-huset, Universitetssjukhuset i Örebro, S Grev Rosengatan 18, 703 62 Örebro, 11:57 (Swedish)
Opponent
Supervisors
Available from: 2013-10-29 Created: 2013-10-29 Last updated: 2017-10-17Bibliographically approved

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Hussain, RashidaRoomans, Godfried M.
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School of Health and Medical Sciences, Örebro University, SwedenSchool of Medicine, Örebro University, Sweden
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