ß1 -adrenergic receptor autoantibodies from heart failure patients enhanced TNF-α secretion in RAW264.7 macrophages in a largely PKA-dependent fashion.
J Cell Biochem
; 113(10): 3218-28, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22628174
ABSTRACT
Autoantibodies against the second extracellular loop of ß(1) -adrenergic receptor (ß(1) -AA) not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their catecholamine-like effects via binding with the ß(1) -adrenergic receptor. The current study was designed to determine whether ß(1) -AA isolated from the sera of heart failure patients could cause TNF-α secretion from the murine macrophage-like cell line RAW264.7. Blood samples were collected from 40 patients who had suffered heart failure, as well as from 40 healthy subjects. The titer of ß(1) -AA and the level of TNF-α were detected using ELISA. The effect of ß(1) -AA on murine macrophage-like cell line RAW264.7 proliferation was detected by CCK-8 kits and CFSE assay. Western blot assay was used to analyze the expression of phospho-VASP. ß(1) -AA appeared more frequently in patients with heart failure than in healthy subjects. The ß(1) -AA isolated from heart failure patients promoted an increase of TNF-α levels, which could be completely blocked by the selective ß(1) -adrenergic receptor antagonist metoprolol and the second extracellular loop of ß(1) -adrenergic receptor (ß(1) -AR-EC(II) ), but only partially inhibited by PKA inhibitor H89. Furthermore, the ß(1) -AA could enhance the proliferation of RAW264.7 cells in vitro. Meanwhile, the expression of phospho-VASP was markedly increased in the presence of ß(1) -AA. These results demonstrate for the first time that the ß(1) -AA isolated from heart failure patients could bind with ß(1) -AR on the surface of RAW264.7 cells, causing the release of TNF-α largely in a PKA-dependent fashion.
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1
Banco de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
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Factor de Necrosis Tumoral alfa
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Receptores Adrenérgicos beta 1
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Proteínas Quinasas Dependientes de AMP Cíclico
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Insuficiencia Cardíaca
Tipo de estudio:
Observational_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article