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Decreased expression of Nod2-receptors and production of pro-inflammatory cytokines in cystic fibrosis airway epithelial cells
Örebro universitet, Hälsoakademin.
Örebro universitet, Hälsoakademin.
Örebro universitet, Hälsoakademin.
Örebro university hospital, Department of pediatrics.
Vise andre og tillknytning
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Forskningsprogram
Medicin
Identifikatorer
URN: urn:nbn:se:oru:diva-20479OAI: oai:DiVA.org:oru-20479DiVA, id: diva2:461553
Tilgjengelig fra: 2011-12-05 Laget: 2011-12-05 Sist oppdatert: 2017-10-17bibliografisk kontrollert
Inngår i avhandling
1. Chloride transport and inflammation in cystic fibrosis airways
Åpne denne publikasjonen i ny fane eller vindu >>Chloride transport and inflammation in cystic fibrosis airways
2011 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Cystic fibrosis (CF) is one of the most common lethal, autosomal recessive inherited diseases among Caucasians. It is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel activated by cyclic AMP. The disturbed electrolyte transport caused by the impaired CFTR channel leads to defective mucociliary clearance, airway obstruction and chronic airway infections.

Three different substances (N-acetylcysteine, duramycin and ambroxol) were tested in order to investigate if they could improve Cl- transport across epithelia and if so, through which mechanisms.

N-acetylcysteine (NAC), a well-known mucolytic and anti-oxidant drug increased significantly Cl-efflux from cystic fibrosis bronchial epithelial (CFBE) cells. It was shown that NAC can (partially) correct the Cl- transport deficiency in CF airway epithelial cells withF508-CFTR through a direct effect on CFTR (Paper I).

Duramycin increased Cl- efflux from CF airway epithelial cell in a very narrow concentration range. That effect is not associated with an increase in the intracellular calcium concentration (Paper II). The fact that results of a clinical study of duramycin, carried out several years ago, have not been published suggests that duramycin is not only ineffective in vitro, but also in vivo.

Ambroxol has been widely used as supplementary therapy for the treatment of many respiratory diseases. It was shown that 8h treatment with ambroxol caused a nearly six-fold increase of Cl- efflux from CF airway epithelial cells, which brings the Cl- efflux up to the level of cells with wild-type CFTR (Paper III).

Moreover, we studied the role of the innate immunity system in CF airway epithelial cells. High levels of Nod1 were found both in CF and non-CF airway epithelial cells, but a decreased expression of Nod2, and decreased levels of the pro-inflammatory cytokines IL-6 and IL-8 were found in CF airway epithelial cells compared to non-CF cells. The decreased levels of Nod2 suggest that the CF-cells are less able to recognize pathogens such as Pseudomonas aeruginosa, which might lead to a higher uptake of the pathogen (Paper IV).

sted, utgiver, år, opplag, sider
Örebro: Örebro universitet, 2011. s. 65
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 62
Emneord
Cystic fibrosis, CFTR, chloride efflux, N-acetylcysteine, ambroxol, duramycin, Nod-like receptors, cytokines
HSV kategori
Forskningsprogram
Medicin
Identifikatorer
urn:nbn:se:oru:diva-19126 (URN)978-91-7668-830-4 (ISBN)
Disputas
2011-11-25, Seminarierum Berguven (F1), Universitetssjukhuset, Örebro, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2011-10-04 Laget: 2011-10-04 Sist oppdatert: 2017-10-17bibliografisk kontrollert

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