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Abstract/Summary
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<jats:title>Abstract</jats:title><jats:p>Inflammatory airway diseases like cystic fibrosis, asthma and COVID-19 are characterized by high levels of pulmonary cytokines. Two well-established antiparasitic drugs, niclosamide and ivermectin, are intensively discussed for the treatment of viral inflammatory airway infections. Here, we examined these repurposed drugs with respect to their anti-inflammatory effects in airways <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic>. Niclosamide reduced mucus content, eosinophilic infiltration and cell death in asthmatic mouse lungs <jats:italic>in vivo</jats:italic> and inhibited release of interleukins in the two differentiated airway epithelial cell lines CFBE and BCi-NS1.1 <jats:italic>in vitro</jats:italic>. Cytokine release was also inhibited by the knockdown of the Ca<jats:sup>2+</jats:sup>-activated Cl<jats:sup>−</jats:sup> channel anoctamin 1 (ANO1, TMEM16A) and the phospholipid scramblase anoctamin 6 (ANO6, TMEM16F), which have previously been shown to affect intracellular Ca<jats:sup>2+</jats:sup> levels near the plasma membrane and to facilitate exocytosis. At concentrations around 200 nM, niclosamide inhibited inflammation, lowered intracellular Ca<jats:sup>2+</jats:sup>, acidified cytosolic pH and blocked activation of ANO1 and ANO6. It is suggested that niclosamide brings about its anti-inflammatory effects at least in part by inhibiting ANO1 and ANO6, and by lowering intracellular Ca<jats:sup>2+</jats:sup> levels. In contrast to niclosamide, 1 µM ivermectin did not exert any of the effects described for niclosamide. The present data suggest niclosamide as an effective anti-inflammatory treatment in CF, asthma, and COVID-19, in addition to its previously reported antiviral effects. It has an advantageous concentration–response relationship and is known to be well tolerated.</jats:p>
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Hinweis
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DeepGreen-ID: c087d0273838446a80c098d83559ebf6 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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