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SHR Neuro Krebs Kardio Lipid Stoffw Microb
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. 2020; 75(2):392-402
Doi: 10.1111/all.14022
[OPEN ACCESS]
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Böhm Eva
- Roula David
- Co-Autor*innen der Med Uni Graz
- Heinemann Akos
- Luschnig Petra
- Marsche Gunther
- 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 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. 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. © 2019 The Authors. Allergy published by John Wiley & Sons Ltd.
- 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