Dataset Information

?1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the ?1-AR/cAMP/PKA and p38 MAPK pathways.

ABSTRACT:

Background

Autoantibodies against the second extracellular loop of the ?(1)-adrenergic receptor (?(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 ?(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 ?(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 ?(1)-AA was detected using ELISA. The CD3(+)T lymphocytes were selected separately through flow cytometry and the effect of ?(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

?(1)-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective ?(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 ?(1)-AA. ?(1)-AA also inhibited the secretion of interferon-? (IFN-?) while promoting an increase in interleukin-4 (IL-4) levels.

Conclusions

These results demonstrate that ?(1)-AA isolated from DCM patients binds to ?(1)-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the ?(1)-AR/cAMP/PKA and p38 MAPK pathways.

SUBMITTER: Du Y

PROVIDER: S-EPMC3534136 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

β1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the β1-AR/cAMP/PKA and p38 MAPK pathways.

Du Yunhui Y Yan Li L Wang Jin J Zhan Wenzhang W Song Kai K Han Xue X Li Xiao X Cao Jimin J Liu Huirong H

PloS one 20121231 12

<h4>Background</h4>Autoantibodies against the second extracellular loop of the β(1)-adrenergic receptor (β(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 β(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 β(1)-AA isola ...[more]

PMID: 23300817

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