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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.
Roula, David; Theiler, Anna; Luschnig, Petra; Sturm, Gunter J; Tomazic, Peter V; Marsche, Gunther; Heinemann, Akos; Sturm, Eva M.
Afiliación
  • Roula D; Division of Pharmacology, Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
  • Theiler A; Division of Pharmacology, Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
  • Luschnig P; Division of Pharmacology, Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
  • Sturm GJ; Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.
  • Tomazic PV; Allergy Outpatient Clinic Reumannplatz, Vienna, Austria.
  • Marsche G; ENT-University Hospital, Medical University of Graz, Graz, Austria.
  • Heinemann A; Division of Pharmacology, Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
  • Sturm EM; Division of Pharmacology, Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
Allergy ; 75(2): 392-402, 2020 02.
Article en En | MEDLINE | ID: mdl-31408538
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, 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. RESULTS: 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. 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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apolipoproteínas A / Asma / Sinusitis / Rinitis / Antiinflamatorios Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Allergy Año: 2020 Tipo del documento: Article País de afiliación: Austria

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apolipoproteínas A / Asma / Sinusitis / Rinitis / Antiinflamatorios Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Allergy Año: 2020 Tipo del documento: Article País de afiliación: Austria