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Quinolines is a group of small heterocyclic compounds that have a broad range of pharmacological properties. Here, we investigated the airway relaxant and anti-inflammatory properties of a novel quinoline (RCD405).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The airway relaxant effect of RCD405 was examined in isolated airways from humans, dogs, rats and mice. Murine models of ovalbumin (OVA)-induced allergic asthma and LPS-induced airway inflammation were used to study the effects in vivo. RCD405 (10\u00a0mg\/kg) or, for comparisons in selected studies, budesonide (3\u00a0mg\/kg), were administered intratracheally 1\u00a0h prior to each challenge. Airway responsiveness was determined using methacholine provocation. Immune cell recruitment to bronchi was measured using flow cytometry and histological analyses were applied to investigate cell influx and goblet cell hyperplasia of the airways. Furthermore, production of cytokines and chemokines was measured using a multiplex immunoassay. The expression levels of asthma-related genes in murine lung tissue were determined by PCR. The involvement of NF-\u03baB and metabolic activity was measured in the human monocytic cell line THP-1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RCD405 demonstrated a relaxant effect on carbachol precontracted airways in all four species investigated (potency ranking: human\u2009=\u2009rat\u2009&gt;\u2009dog\u2009=\u2009mouse). The OVA-specific IgE and airway hyperresponsiveness (AHR) were significantly reduced by intratracheal treatment with RCD405, while no significant changes were observed for budesonide. In addition, administration of RCD405 to mice significantly decreased the expression of proinflammatory cytokines and chemokines as well as recruitment of immune cells to the lungs in both OVA- and LPS-induced airway inflammation, with a similar effect as for budesonide (in the OVA-model). However, the effect on gene expression of\n                      <jats:italic>Il-4, IL-5<\/jats:italic>\n                      and\n                      <jats:italic>Il-13<\/jats:italic>\n                      was more pronounced for RCD405 as compared to budesonide. Finally, in vitro, RCD405 reduced the LPS-induced NF-\u03baB activation and by itself reduced cellular metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RCD405 has airway relaxant effects, and it reduces AHR as well as airway inflammation in the models used, suggesting that it could be a clinically relevant compound to treat inflammatory airway diseases. Possible targets of this compound are complexes of mitochondrial oxidative phosphorylation, resulting in decreased metabolic activity of targeted cells as well as through pathways associated to NF-\u03baB. However, further studies are needed to elucidate the mode of action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-024-02780-8","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T14:01:46Z","timestamp":1711807306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A novel quinoline with airway relaxant effects and anti-inflammatory properties"],"prefix":"10.1186","volume":"25","author":[{"given":"Jesper","family":"Bergwik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jielu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9dea","family":"Padra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi K. 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Inflamm Res. 2013;62:367\u201376.","journal-title":"Inflamm Res"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-024-02780-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-024-02780-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-024-02780-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T14:02:11Z","timestamp":1711807331000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-024-02780-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,30]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2780"],"URL":"https:\/\/doi.org\/10.1186\/s12931-024-02780-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3480865\/v1","asserted-by":"object"}]},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,30]]},"assertion":[{"value":"23 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures involving human tissue were in accordance with the ethical standards of the relevant institution and\/or national research committee of each collection site, REPROCELL\u2019s ethical approval for use of human tissue (West of Scotland Research Ethics Service 17\/WS\/0049), and the amended Helsinki Declaration. Informed written consent was obtained from all individual participants or their nominated persons. Procedures involving rat and dog tissues were performed in accordance with the UK Animal Welfare Act 2006. Murine experiments were approved by the Malm\u00f6-Lund Animal Care Ethics Committee (ethical permit no. 3802-19) and the Stockholm Animal Care Ethics Committee (ethical permit no. 3649-2019).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A joint grant from VINNOVA was provided to Arcede Pharma AB and AE as mentioned above. AE has received a honorar as an advisor from Arcede Pharma AB that holds a patent for RCD405. MA has received funding from Arcede Pharma AB to conduct experiments for the study. ML is employed by Arcede Pharma AB.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"146"}}