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Johannesson, Marie
Publications (9 of 9) Show all publications
Varelogianni, G., Hussain, R., Strid, H., Oliynyk, I., Roomans, G. M. & Johannesson, M. (2013). The effect of ambroxol on chloride transport, CFTR and ENaC in cysticfibrosis airway epithelial cells. Cell Biology International, 37(11), 1149-1156
Open this publication in new window or tab >>The effect of ambroxol on chloride transport, CFTR and ENaC in cysticfibrosis airway epithelial cells
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2013 (English)In: Cell Biology International, ISSN 1065-6995, E-ISSN 1095-8355, Vol. 37, no 11, p. 1149-1156Article in journal (Refereed) Published
Abstract [en]

Ambroxol, a mucokinetic anti-inflammatory drug, has been used for treatment of cystic fibrosis (CF). The respiratoryepitheliumis covered by the airway surface liquid (ASL), the thickness and composition of which is determined by Cl efflux viathe cystic fibrosis transmembrane conductance regulator (CFTR) and Naþ influx via the epithelial Naþ channel (ENaC). In cellsexpressing wt-CFTR, ambroxol increased the Cl- conductance, but not the bicarbonate conductance of the CFTR channels.Weinvestigated whether treatment with ambroxol enhances chloride transport and/or CFTR and ENaC expression in CF airwayepithelial cells (CFBE) cells. CFBE cells were treated with 100 mM ambroxol for 2, 4 or 8 h. mRNA expression for CFTR andENaC subunits was analysed by real-time polymerase chain reaction (RT-PCR); protein expression was measured by Westernblot. The effect of ambroxol on Cl− transport was measured by Cl− efflux measurements with a fluorescent chloride probe.Ambroxol significantly stimulated Cl− efflux from CFBE cells (a sixfold increase after 8 h treatment), and enhanced theexpression of the mRNA of CFTR and a-ENaC, and of the CFTR protein. No significant difference was observed in b-ENaCafter exposure to ambroxol, whereasmRNA expression of g-ENaC was reduced. No significant effects of ambroxol on the ENaCsubunits were observed by Western blot. Ambroxol did not significantly affect the intracellular Ca2+ concentration.Upregulation of CFTR and enhanced Cl efflux after ambroxol treatment should promote transepithelial ion and watertransport, which may improve hydration of the mucus, and therefore be beneficial to CF-patients.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2013
Keywords
Airway epithelium, ambroxol, cystic fibrosis, Cl− efflux, CFTR; ENaC
National Category
Medical and Health Sciences Cell Biology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-32769 (URN)10.1002/cbin.10146 (DOI)000325489500002 ()23765701 (PubMedID)2-s2.0-84885861654 (Scopus ID)
External cooperation:
Funder
Swedish Heart Lung FoundationSwedish Research Council
Note

Funding Agencies:

Swedish Science Research Council 

Available from: 2013-12-13 Created: 2013-12-13 Last updated: 2017-12-06Bibliographically approved
Oliynyk, I., Hussain, R., Amin, A., Johannesson, M. & Roomans, G. M. (2013). The effect of NO-donors on chloride efflux, intracellular Ca2+ concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells. Experimental and molecular pathology (Print), 94(3), 474-480
Open this publication in new window or tab >>The effect of NO-donors on chloride efflux, intracellular Ca2+ concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells
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2013 (English)In: Experimental and molecular pathology (Print), ISSN 0014-4800, E-ISSN 1096-0945, Vol. 94, no 3, p. 474-480Article in journal (Refereed) Published
Abstract [en]

Since previous studies showed that the endogenous bronchodilator, S nitrosglutathione (GSNO), caused amarked increase in CFTR-mediated chloride (Cl−) efflux and improved the trafficking of CFTR to the plasmamembrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl− efflux, itwas investigatedwhether the NO-donor properties of GSNOwere relevant for its effect on Cl− efflux fromairwayepithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-Nacetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitricoxide adduct (DEA-NONOate) on Cl− efflux from CFBE (ΔF508/ΔF508-CFTR) airway epithelial cells was tested.Cl− efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide(MQAE)-technique. Possible changes in the intracellular Ca2+ concentration were tested by the fluorescent fluo-4method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, anincreased Cl− efflux was found (in the order SNAP > DETA-NO > SNP). The effect of DEA-NONOate on Cl− effluxwas not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as withGSNO, after a short (5 min) incubation, SNP had no significant effect on Cl− efflux. None of the NO-donors thathad a significant effect on Cl− efflux caused significant changes in the intracellular Ca2+ concentration. After 4 hpreincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOatedecreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only inα-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on theexpression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concludedthat the effect of GSNO on Cl−efflux is, at least in part, due to its properties as an NO-donor, and the effect is likely tobe mediated by CFTR, not by Ca2+-activated Cl− channels.

Place, publisher, year, edition, pages
Maryland Heights, USA: Elsevier, 2013
Keywords
Nitric oxide donors, Cystic fibrosis, Airway epithelium, CFTR, ENaC, Calcium
National Category
Medical and Health Sciences Cell Biology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-32767 (URN)10.1016/j.yexmp.2013.03.003 (DOI)000319535900008 ()23523754 (PubMedID)2-s2.0-84876344605 (Scopus ID)
Funder
Swedish Heart Lung FoundationNIH (National Institute of Health)Swedish Research Council
Available from: 2013-12-13 Created: 2013-12-13 Last updated: 2017-12-06Bibliographically approved
Nilsson, H. E., Dragomir, A., Lazorova, L., Johannesson, M. & Roomans, G. M. (2010). CFTR and tight junctions in cultured bronchial epithelial cells. Experimental and molecular pathology (Print), 88(1), 118-127
Open this publication in new window or tab >>CFTR and tight junctions in cultured bronchial epithelial cells
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2010 (English)In: Experimental and molecular pathology (Print), ISSN 0014-4800, E-ISSN 1096-0945, Vol. 88, no 1, p. 118-127Article in journal (Refereed) Published
Abstract [en]

Airway epithelial salt and water transport takes place through paracellular and transcellular pathways. This transport depends critically on the epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane conductance regulator (CFTR), operating in concert with the paracellular pathway through the tight junctions (TJ). Normal (16HBE14o-), cystic fibrosis (CFBE41o-), and corrected CFBE41o- (CFBE41o-pCep4 overexpressing wtCFTR) airway epithelial cell lines were cultured under isotonic conditions. Transepithelial electrical resistance (TEER) was measured as indicator of the tightness of the cultures. Morphology was investigated by immunofluorescence and paracellular permeability by lanthanum nitrate or [C-14] mannitol as permeability markers. The CFTR-defective cell line CFBE41o- developed higher TEER than its corrected counterpart CFBE41o-pCep4. Addition of a specific inhibitor of CFTR (CFTRinh-172) to 16HBE14o- and CFBE41o-pCep4 cells resulted in a time-dependent increase in TEER, whereas stimulation of CFTR by IBMX and forskolin caused a decrease. Permeability to lanthanum and [C-14] mannitol was lower in CFBE41o- and in 16HBE14o- cells exposed to CFTRinh-172, compared to untreated 16HBE14o- and CFBE41o-pCep4 cells, respectively. 16HBE14o- cells exposed to IBMX and forskolin showed higher permeability to lanthanum but lower permeability to [C-14] mannitol compared to control. Immunofluorescence revealed a disorganization of F-actin and alpha-tubulin in 16HBE14o- cells and CFBE41o- pCep4 exposed to CFTRinh-172 and in CFBE41o- cells. Changes in F-actin and alpha-tubulin in 16HBE14o- cells exposed to IBMX and forskolin were also seen. These results suggest the possibility of an interaction between CFTR and the TJ protein complex, probably via the cytoskeleton. (C) 2009 Elsevier Inc. All rights reserved.

Keywords
CFTR, Transepithelial electrical resistance, Tight junctions, Cytoskeleton
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-13020 (URN)10.1016/j.yexmp.2009.09.018 (DOI)000274500100017 ()
Available from: 2011-01-03 Created: 2011-01-03 Last updated: 2017-12-11Bibliographically approved
Bahmanyar, S., Ekbom, A., Askling, J., Johannesson, M. & Montgomery, S. M. (2010). Cystic fibrosis gene mutations and gastrointestinal diseases. Journal of Cystic Fibrosis, 9(4), 288-291
Open this publication in new window or tab >>Cystic fibrosis gene mutations and gastrointestinal diseases
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2010 (English)In: Journal of Cystic Fibrosis, ISSN 1569-1993, E-ISSN 1873-5010, Vol. 9, no 4, p. 288-291Article in journal (Refereed) Published
Abstract [en]

Background: This study examined if CF mutation heterozygosity is associated with diseases of gastrointestinal epithelial barrier function. Design and methods: Swedish registers identified 865 patients with a diagnosis of CF between 1968 and 2003 and matched with 8101 individuals without CF. Gastrointestinal disease risk was examined among 1534 biological parents and 1396 siblings of CF patients, compared with 15,526 parents and 15,542 siblings of individuals without CF. Results: First-degree relatives of CF patients were not at lower risk of the gastrointestinal diseases, in contrast with a raised risk among CF patients. Conclusion: Heterozygosity for CF gene mutations does not protect against gastrointestinal diseases where impaired barrier function may be relevant. (C) 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Keywords
Cystic fibrosis, Gene mutation, Gastrointestinal diseases, Barrier function
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-25549 (URN)10.1016/j.jcf.2010.03.010 (DOI)000280009500011 ()
Available from: 2012-08-29 Created: 2012-08-29 Last updated: 2018-07-22Bibliographically approved
Oliynyk, I., Varelogianni, G., Roomans, G. M. & Johannesson, M. (2010). Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 118(12), 982-990
Open this publication in new window or tab >>Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia
2010 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, no 12, p. 982-990Article in journal (Refereed) Published
Abstract [en]

The lantibiotic duramycin (Moli1901, Lancovutide) has been suggested as a drug of choice in the treatment for cystic fibrosis (CF). It has been proposed that duramycin may stimulate chloride secretion through Ca2+-activated Cl channels (CaCC). We investigated whether duramycin exhibited any effect on Cl efflux and intracellular Ca2+ concentration ([Ca2+]i) in CF and non-CF epithelial cells. Duramycin did stimulate Cl efflux from CF bronchial epithelial cells (CFBE) in a narrow concentration range (around 1 μM). However, 100 and 250 μM of duramycin inhibited Cl efflux from CFBE cells. An inhibitor of the CF transmembrane conductance regulator (CFTRinh-172) and a blocker of the capacitative Ca2+ entry, gadolinium chloride, inhibited the duramycin-induced Cl efflux. No effect on Cl efflux was observed in non-CF human bronchial epithelial cells (16HBE), human airway submucosal gland cell line, human pancreatic epithelial cells, CF airway submucosal gland epithelial cells, and CF pancreatic cells. The [Ca2+]i was increased by 3 μM duramycin in 16HBE cells, but decreased after 1, and 3 μM of duramycin in CFBE cells. The results suggest that the mechanism responsible for the stimulation of Cl efflux by duramycin is mainly related to unspecific changes of the cell membrane or its components rather than to effects on CaCC.

Place, publisher, year, edition, pages
New York, USA: John Wiley & Sons, 2010
Keywords
Duramycin, cystic fibrosis, airway epithelium, chloride efflux
National Category
Medical and Health Sciences Immunology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-12442 (URN)10.1111/j.1600-0463.2010.02680.x (DOI)000284317500010 ()21091780 (PubMedID)2-s2.0-78649506897 (Scopus ID)
Available from: 2010-11-11 Created: 2010-11-11 Last updated: 2018-04-19Bibliographically approved
Varelogianni, G., Oliynyk, I., Roomans, G. M. & Johannesson, M. (2010). The effect of N-acetylcysteine on chloride efflux from airway epithelial cells. Cell Biology International, 34(3), 245-252
Open this publication in new window or tab >>The effect of N-acetylcysteine on chloride efflux from airway epithelial cells
2010 (English)In: Cell Biology International, ISSN 1065-6995, E-ISSN 1095-8355, Vol. 34, no 3, p. 245-252Article in journal (Refereed) Published
Abstract [en]

Defective chloride transport in epithelial cells increases mucus viscosity and leads to recurrent infections with high oxidative stress in patients with CF (cystic fibrosis). NAC (N-acetylcysteine) is a well known mucolytic and antioxidant drug, and an indirect precursor of glutathione. Since GSNO (S-nitrosoglutathione) previously has been shown to be able to promote Cl efflux from CF airway epithelial cells, it was investigated whether NAC also could stimulate Cl efflux from CF and non-CF epithelial cells and through which mechanisms. CFBE (CF bronchial epithelial cells) and normal bronchial epithelial cells (16HBE) were treated with 1 mM, 5 mM, 10 mM or 15 mM NAC for 4 h at 37°C. The effect of NAC on Cl transport was measured by Cl efflux measurements and by X-ray microanalysis. Cl efflux from CFBE cells was stimulated by NAC in a dose-dependent manner, with 10 mM NAC causing a significant increase in Cl efflux with nearly 80% in CFBE cells. The intracellular Cl concentration in CFBE cells was significantly decreased up to 60% after 4 h treatment with 10 mM NAC. Moreover immunocytochemistry and Western blot experiments revealed expression of CFTR channel on CFBE cells after treatment with 10 mM NAC. The stimulation of Cl efflux by NAC in CF airway epithelial cells may improve hydration of the mucus and thereby be beneficial for CF patients.

Place, publisher, year, edition, pages
London: Portland Press Ltd, 2010
Keywords
airway epithelium, chloride transport, cystic fibrosis, N-acetylcysteine, Medical cell biology, Morphology, cell biology, pathology
National Category
Cell and Molecular Biology Medical and Health Sciences Cell and Molecular Biology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-12451 (URN)10.1042/CBI20090007 (DOI)000277391600002 ()
Note

Georgia Varelogianni, Igor Oliynyk, Godfried M Roomans are also affiliated w. Department of Medical Cell Biology, Uppsala University, Box 571, SE-75123 Uppsala, Sweden

Available from: 2010-11-12 Created: 2010-11-12 Last updated: 2018-04-19Bibliographically approved
Oliynyk, I., Varelogianni, G., Schalling, M., Stenkvist Asplund, M., Roomans, G. M. & Johannesson, M. (2009). Azithromycin increases chloride efflux from cystic fibrosis airway epithelial cells. Experimental Lung Research, 35(3), 210-221
Open this publication in new window or tab >>Azithromycin increases chloride efflux from cystic fibrosis airway epithelial cells
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2009 (English)In: Experimental Lung Research, ISSN 0190-2148, E-ISSN 1521-0499, Vol. 35, no 3, p. 210-221Article in journal (Refereed) Published
Abstract [en]

It was investigated whether azithromycin (AZM) stimulates chloride (Cl−) efflux from cystic fibrosis (CF) and non-CF airway epithelial cells, possibly secondary to up-regulation of the multidrug resistance protein (MDR). CF and non-CF human airway epithelial cell lines (CFBE and 16HBE) were treated with 0.4, 4, and 40 μ g/mL AZM for 4 days. Cl− efflux was explored in the presence or absence of specific inhibitors of CFTR and alternative Cl−  channels. Six CF patients received AZM (500 mg daily) for 6 months. The percentage of predicted forced vital capacity (FVC%), forced expiratory volume (FEV1%), and the number of acute exacerbations were compared before and after treatment. Nasal biopsies were taken before and after treatment, and mRNA expression of MDR and CFTR was determined by in situ hybridization. A significant dose-dependent increase of Cl− efflux from CFBE cells (but not from 16HBE cells) was observed after AZM treatment. A CFTR inhibitor significantly reduced AZM-stimulated Cl−  efflux from CFBE cells. A significant improvement in FEV1%, and fewer exacerbations were observed. AZM treatment did not affect mRNA expression of MDR and CFTR. The stimulation of Cl− efflux could be part of the explanation for the clinical improvement seen among the patients.

Place, publisher, year, edition, pages
Taylor & Francis, 2009
Keywords
azithromycin, chloride transport, cystic fibrosis, lung function, Morphology, Medical cell biology, pathology
National Category
Medical and Health Sciences Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-12440 (URN)10.1080/01902140802534967 (DOI)000264750200004 ()19337904 (PubMedID)2-s2.0-67149144260 (Scopus ID)
Available from: 2010-11-11 Created: 2010-11-11 Last updated: 2017-12-12Bibliographically approved
Johannesson, M., Askling, J., Montgomery, S. M., Ekbom, A. & Bahmanyar, S. (2009). Cancer risk among patients with cystic fibrosis and their first-degree relatives. International Journal of Cancer, 125(12), 2953-2956
Open this publication in new window or tab >>Cancer risk among patients with cystic fibrosis and their first-degree relatives
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2009 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, no 12, p. 2953-2956Article in journal (Refereed) Published
Abstract [en]

Patients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population-based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first-degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95% CI 2.1-4.6). We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow-up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk.

National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-11991 (URN)10.1002/ijc.24679 (DOI)19551859 (PubMedID)
Available from: 2010-10-04 Created: 2010-10-04 Last updated: 2017-12-12Bibliographically approved
Varelogianni, G., Strid, H., Oliynyk, I., Roomans, G. M. & Johannesson, M.The effect of ambroxol on chloride transport and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells.
Open this publication in new window or tab >>The effect of ambroxol on chloride transport and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-20478 (URN)
Available from: 2011-12-05 Created: 2011-12-05 Last updated: 2017-10-17Bibliographically approved
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