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Apolipoprotein A‐IV acts as an endogenous anti‐inflammatory protein and is reduced in treatment‐naïve allergic patients and allergen‐challenged mice
Author(s) -
Roula David,
Theiler Anna,
Luschnig Petra,
Sturm Gunter J.,
Tomazic Peter V.,
Marsche Gunther,
Heinemann Akos,
Sturm Eva M.
Publication year - 2020
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14022
Subject(s) - eosinophil , immunology , allergic inflammation , eosinophilia , inflammation , medicine , major basic protein , eosinophil cationic protein , asthma
Background Recent studies pointed to a crucial role for apolipoproteins in the pathogenesis of inflammatory diseases. However, the role of apolipoprotein‐IV (ApoA‐IV) in allergic inflammation has not been addressed thoroughly thus far. Objective Here, we explored the anti‐inflammatory effects and underlying signaling pathways of ApoA‐IV on eosinophil effector function in vitro and in vivo. Methods Migratory responsiveness, Ca 2+ ‐flux and apoptosis of human peripheral blood eosinophils were assessed in vitro. Allergen‐driven airway inflammation was assessed in a mouse model of acute house dust mite‐induced asthma. ApoA‐IV serum levels were determined by ELISA. Results Recombinant ApoA‐IV potently inhibited eosinophil responsiveness in vitro as measured by Ca 2+ ‐flux, shape change, integrin (CD11b) expression, and chemotaxis. The underlying molecular mechanism involved the activation of Rev‐ErbA‐α and induced a PI3K/PDK1/PKA‐dependent signaling cascade. Systemic application of ApoA‐IV prevented airway hyperresponsiveness (AHR) and airway eosinophilia in mice following allergen challenge. ApoA‐IV levels were decreased in serum from allergic patients compared to healthy controls. Conclusion Our data suggest that ApoA‐IV is an endogenous anti‐inflammatory protein that potently suppresses effector cell functions in eosinophils. Thus, exogenously applied ApoA‐IV may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophil‐driven disorders.