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beta1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the beta1-AR/cAMP/PKA and p38 MAPK pathways #MMPMID23300817
Du Y; Yan L; Wang J; Zhan W; Song K; Han X; Li X; Cao J; Liu H
PLoS One 2012[]; 7 (12): e52911 PMID23300817show ga
BACKGROUND: Autoantibodies against the second extracellular loop of the beta(1)-adrenergic receptor (beta(1)-AA) not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their sympathomimetic-like effects that are induced upon binding to the beta(1)-adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether beta(1)-AA isolated from the sera of dilated cardiomyopathy (DCM) patients caused the proliferation of T cells and the secretion of cytokines. METHODS: Blood samples were collected from 95 DCM patients as well as 95 healthy subjects, and beta(1)-AA was detected using ELISA. The CD3(+)T lymphocytes were selected separately through flow cytometry and the effect of beta(1)-AA on T lymphocyte proliferation was examined by CCK-8 kits and CFSE assay. Western blotting was used to analyze the expressions of phospho-VASP and phospho-p38 MAPK. RESULTS: beta(1)-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective beta(1)-adrenergic receptor antagonist metoprolol, PKA inhibitor H89, and p38 MAPK inhibitor SB203580. Furthermore, the expression of the phosphorylated forms of phospho-VASP and phospho-p38 MAPK were markedly increased in the presence of beta(1)-AA. beta(1)-AA also inhibited the secretion of interferon-gamma (IFN-gamma) while promoting an increase in interleukin-4 (IL-4) levels. CONCLUSIONS: These results demonstrate that beta(1)-AA isolated from DCM patients binds to beta(1)-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the beta(1)-AR/cAMP/PKA and p38 MAPK pathways.
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PLoS+One 2012 ; 7 (12): e52911
