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Modulation of ENaC, CFTR, and iNOS expression in bronchial epithelial cells after stimulation with Staphylococcus epidermidis (94B080) and Staphylococcus aureus (90B083)
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0003-4946-3228
School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Pediatrics, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
2013 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 9, p. 814-826Article in journal (Refereed) Published
Abstract [en]

Bacteria affect the respiratory epithelium, which is covered by airway surface liquid (ASL) and mucus. Ion concentrations in the ASL are determined by the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC). Neonatal sepsis is a major risk factor for subsequent pulmonary disease in preterm newborns. Predominating are coagulase-negative staphylococci (e.g., Staphylococccus epidermidis and Staphylococccus aureus). The aim of this study was to investigate modulation of CFTR, ENaC, mucins, proinflammatory cytokines, and inducible nitric oxide synthase (iNOS) in respiratory epithelial cells after S. epidermidis 94B080 and S. aureus 90B083 exposure. Bronchial epithelial cells were incubated with S. epidermidis 94B080 and S. aureus 90B083 (neonatal blood isolates) for 1-36h. Expression of CFTR, ENaC, iNOS, and mucins was analyzed by real-time PCR and Western blotting. Release of cytokines was analyzed by ELISA, and production of NO by the Griess assay. Expression of CFTR significantly decreased after 36h incubation with S. epidermidis and more prominently with S. aureus, whereas S. epidermidis caused a significant increase in the expression of - and -ENaC. Expression of iNOS increased, but NO was not detected. Both staphylococci caused a decrease in the intracellular Ca2+ concentration. S. aureus induced increased secretion of IL-6, IL-8, and transforming nuclear factor (TNF)- in a time-dependent manner as compared with S. epidermidis. In conclusion, expression of ENaC, CFTR, and iNOS is modulated by exposure to S. aureus 90B083 and S. epidermidis 94B080. S. aureus is more potent in causing release of IL-6, IL-8, and TNF- by bronchial epithelial cells as compared with S. epidermidis. The mRNA expression for the mucus proteins MUC2, MUC5AC, and MUC5B could not be measured, neither in the presence nor in the absence of bacteria.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2013. Vol. 121, no 9, p. 814-826
Keywords [en]
Airway epithelium, Staphylococcus aureus 90B083, Staphylococcus epidermidis 94B080, CFTR, ENaC, iNOS, cytokines
National Category
Medical and Health Sciences Immunology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-30514DOI: 10.1111/apm.12138ISI: 000322757000003PubMedID: 23879620Scopus ID: 2-s2.0-84881558007OAI: oai:DiVA.org:oru-30514DiVA, id: diva2:644382
Note

Funding Agencies:

Nyckelfonden of Örebro University Hospital 

Swedish Science Research Council 

Swedish Heart Lung Foundation 

Available from: 2013-08-30 Created: 2013-08-30 Last updated: 2018-05-21Bibliographically 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. p. 85
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 99
Keywords
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, RashidaOliynyk, IgorRoomans, Godfried M.Björkqvist, Maria

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