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- Title
β<sub>1</sub>-Adrenoceptor Autoantibodies from DCM Patients Enhance the Proliferation of T Lymphocytes through the β<sub>1</sub>-AR/cAMP/PKA and p38 MAPK Pathways.
- Authors
Yunhui Du; Li Yan; Jin Wang; Wenzhang Zhan; Kai Song; Xue Han; Xiao Li; Jimin Cao; Huirong Liu
- Abstract
Background: Autoantibodies against the second extracellular loop of the β1-adrenergic receptor (β1-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 β1-adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether β1-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 β1-AA was detected using ELISA. The CD3+T lymphocytes were selected separately through flow cytometry and the effect of β1-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: β1-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective β1-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 β1-AA. β1-AA also inhibited the secretion of interferon-γ (IFN-γ) while promoting an increase in interleukin-4 (IL-4) levels. Conclusions: These results demonstrate that β1-AA isolated from DCM patients binds to β1-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β1-AR/cAMP/PKA and p38 MAPK pathways.
- Subjects
ADRENERGIC receptors; AUTOANTIBODIES; CELL proliferation; HEART failure; T cells; LYMPHOCYTES
- Publication
PLoS ONE, 2012, Vol 7, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0052911