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However, the role of apolipoprotein\u2010IV (ApoA\u2010IV) in allergic inflammation has not been addressed thoroughly thus far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Here, we explored the anti\u2010inflammatory effects and underlying signaling pathways of ApoA\u2010IV on eosinophil effector function in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Migratory responsiveness, Ca<jats:sup>2+<\/jats:sup>\u2010flux and apoptosis of human peripheral blood eosinophils were assessed in vitro. Allergen\u2010driven airway inflammation was assessed in a mouse model of acute house dust mite\u2010induced asthma. ApoA\u2010IV serum levels were determined by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Recombinant ApoA\u2010IV potently inhibited eosinophil responsiveness in vitro as measured by Ca<jats:sup>2+<\/jats:sup>\u2010flux, shape change, integrin (CD11b) expression, and chemotaxis. The underlying molecular mechanism involved the activation of Rev\u2010ErbA\u2010\u03b1 and induced a PI3K\/PDK1\/PKA\u2010dependent signaling cascade. Systemic application of ApoA\u2010IV prevented airway hyperresponsiveness (AHR) and airway eosinophilia in mice following allergen challenge. ApoA\u2010IV levels were decreased in serum from allergic patients compared to healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that ApoA\u2010IV is an endogenous anti\u2010inflammatory protein that potently suppresses effector cell functions in eosinophils. Thus, exogenously applied ApoA\u2010IV may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophil\u2010driven disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14022","type":"journal-article","created":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T18:54:10Z","timestamp":1565722450000},"page":"392-402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Apolipoprotein A\u2010IV acts as an endogenous anti\u2010inflammatory protein and is reduced in treatment\u2010na\u00efve allergic patients and allergen\u2010challenged mice"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0472-6784","authenticated-orcid":false,"given":"David","family":"Roula","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Otto\u2010Loewi Research Center for Vascular Biology, Immunology and Inflammation Medical University of Graz Graz 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