Pinelopi Anagnostopoulou

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (5)31.79 Total impact

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    ABSTRACT: Asthma is a chronic condition with unknown pathogenesis, and recent evidence suggests that enhanced airway epithelial chloride (Cl-) secretion plays a role in the disease. However, the molecular mechanism underlying Cl- secretion and its relevance in asthma pathophysiology remain unknown. To determine the role of the solute carrier family 26, member 9 (SLC26A9) Cl- channel in asthma, we induced Th2-mediated inflammation via IL-13 treatment in wild-type and Slc26a9-deficient mice and compared the effects on airway ion transport, morphology, and mucus content. We found that IL-13 treatment increased Cl- secretion in the airways of wild-type but not Slc26a9-deficient mice. While IL-13-induced mucus overproduction was similar in both strains, treated Slc26a9-deficient mice exhibited airway mucus obstruction, which did not occur in wild-type controls. In a study involving healthy children and asthmatics, a polymorphism in the 3' UTR of SLC26A9 that reduced protein expression in vitro was associated with asthma. Our data demonstrate that the SLC26A9 Cl- channel is activated in airway inflammation and suggest that SLC26A9-mediated Cl- secretion is essential for preventing airway obstruction in allergic airway disease. These results indicate that SLC26A9 may serve as a therapeutic target for airway diseases associated with mucus plugging.
    The Journal of clinical investigation 09/2012; 122(10):3629-34. DOI:10.1172/JCI60429 · 13.22 Impact Factor
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    P. Anagnostopoulou · B. Riederer · J. Duerr · X. Liu · K. Kalitzki · F. Xiao · M. Chen · J. Schatterny · M. Soleimani · U. Seidler · M.A. Mall ·

    Journal of Cystic Fibrosis 06/2012; 11. DOI:10.1016/S1569-1993(12)60017-4 · 3.48 Impact Factor
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    ABSTRACT: Ca(2+)-activated Cl(-) channels (CaCCs) contribute to airway Cl(-) and fluid secretion, and were implicated in the modulation of disease severity and as a therapeutic target in cystic fibrosis (CF). Previous in vitro studies suggested that members of the CLCA gene family, including the murine mCLCA3, contribute to CaCCs. However, the role of mCLCA3 in ion transport in native airway epithelia has not been studied, to the best of our knowledge. In this study, we used mCLCA3-deficient mice and determined bioelectric properties in freshly excised tracheal tissue, airway morphology, and gene expression studies, to determine the role of mCLCA3 in airway ion transport and airway structure. Bioelectric measurements did not detect any differences in basal short-circuit current, amiloride-sensitive Na(+) absorption, cyclic adenosine monophosphate-dependent Cl(-) secretion, and activation of Ca(2+)-activated (uridine-5'-triphosphate-mediated) Cl(-) secretion in mCLCA3-deficient mice compared with wild-type mice. Moreover, no histological changes were observed in the respiratory tract or any other tissues of mCLCA3-deficient mice when compared with wild-type control mice. The intratracheal instillation of IL-13 produced an approximately 30-fold up-regulation of mCLCA3 transcripts without inducing CaCC activity in wild-type airways, and induced goblet-cell hyperplasia and mucin gene expression to similar levels in both genotypes. Further, multiple specific reverse-transcriptase quantitative PCR assays for other CaCC candidates, including mCLCA1, mCLCA2, mCLCA4, mCLCA5, mCLCA6, mCLCA7, mBEST1, mBEST2, mCLC4, mTTYH3, and mTMEM16A, failed to identify the differential expression of genes in the respiratory tract that may compensate for a lack of mCLCA3 function. Together, these findings argue against a role of mCLCA3 in CaCC-mediated Cl(-) secretion in murine respiratory epithelia.
    American Journal of Respiratory Cell and Molecular Biology 02/2012; 47(1):87-93. DOI:10.1165/rcmb.2010-0508OC · 3.99 Impact Factor
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    P Anagnostopoulou · L Dai · J Schatterny · S Hirtz · J Duerr · M A Mall ·
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    ABSTRACT: The airway epithelium is a central effector tissue in allergic inflammation and T-helper cell (Th) type 2-driven epithelial responses, such as mucus hypersecretion contribute to airflow obstruction in allergic airway disease. Previous in vitro studies demonstrated that Th2 cytokines also act as potent modulators of epithelial ion transport and fluid secretion, but the in vivo effect of allergic inflammation on airway ion transport remains unknown. We, therefore, induced allergic inflammation by intratracheal instillation of Aspergillus fumigatus extract or interleukin-13 in mice and determined effects on ion transport in native tracheal and bronchial tissues. We demonstrate that allergic inflammation enhanced basal Cl(-) secretion in both airway regions and inhibited epithelial Na(+) channel (ENaC)-mediated Na(+) absorption and increased Ca²(+)-dependent Cl(-) secretion in bronchi. Allergen-induced alterations in bronchial ion transport were associated with reduced transcript levels of α-, β- and γENaC, and were largely abrogated in signal transducer and activator of transcription (Stat)6(-/-) mice. Our studies demonstrate that Th2-dependent airway inflammation produced a pro-secretory ion transport phenotype in vivo, which was largely Stat6-dependent. These results suggest that Th2-mediated fluid secretion may improve airway surface hydration and clearance of mucus that is hypersecreted in allergic airway diseases such as asthma, and identify epithelial Stat6 signalling as a potential therapeutic target to promote mucus hydration and airway clearance.
    European Respiratory Journal 04/2010; 36(6):1436-47. DOI:10.1183/09031936.00181209 · 7.64 Impact Factor
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    P. Anagnostopoulou · L. Dai · J. Duerr · J. Schatterny · S. Hirtz · M. A. Mall ·

    Journal of Cystic Fibrosis 06/2009; 8. DOI:10.1016/S1569-1993(09)60213-7 · 3.48 Impact Factor