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SHR Neuro Krebs Kardio Lipid

Roula, D; Theiler, A; Luschnig, P; Sturm, GJ; Tomazic, PV; Marsche, G; Heinemann, A; Sturm, EM.
Apolipoprotein A-IV acts as an endogenous anti-inflammatory protein and is reduced in treatment-naïve allergic patients and allergen-challenged mice.
Allergy. 2019; [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Heinemann Akos
Luschnig Petra
Marsche Gunther
Roula David
Sturm Eva
Sturm Gunter
Theiler Anna
Tomazic Peter Valentin
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Abstract:
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. Here we explored the anti-inflammatory effects and underlying signaling pathways of ApoA-IV on eosinophil effector function in vitro and in vivo. Migratory responsiveness, Ca2+ -flux and respiratory burst 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. Recombinant ApoA-IV potently inhibited eosinophil responsiveness in vitro as measured by Ca2+ -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. 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Find related publications in this database (Keywords)
allergic inflammation
apolipoprotein A-IV
chronic rhinosinusitis
eosinophils
house dust mite-induced asthma model
PI3-kinase
Rev-Erb-alpha
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