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Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF- κ B Signaling Pathway

View Article: PubMed Central - PubMed

ABSTRACT

Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear. In this study, we collected human peripheral blood T lymphocytes from patients with AMI and in different stages of percutaneous coronary intervention (PCI) (at the onset of AMI, the first day after PCI (PCI-1), PCI-3, and PCI-5) to study the CaSR and NF-κB pathway protein expression, cytokine release and T cell apoptosis. The results showed that the expressions of CaSR, P-p65, Caspase-12, and the secretions of Th-1 and Th-2 type cytokines were increased at the onset of AMI, especially on the PCI-1. Meanwhile, the apoptosis rate of CD3+, CD4+ and CD8+ T lymphocytes also increased. However, from PCI-3, all the indicators began to decline. In addition, we also found that positive CaSR small interfering RNA (siRNA) transfection in T lymphocytes and NF-κB pathway blocker Bay-11-7082 reversed the increased expressions of CaSR, P-p65, Caspase-12, reduced the secretions of Th-1 and Th-2 type cytokines, and decreased T lymphocytes apoptosis rate not only in the AMI patients but also in the normal controls. All of these results indicated that CaSR in the human peripheral blood T lymphocytes were involved in the AMI onset and progression, which probably was related to the NF-κB pathway. Our study demonstrated the relationship between AMI and CaSR, and will provide new effective prevention theory and new targets for drug treatment.

No MeSH data available.


Expression of P-p65 in the T lymphocytes after CaSR siRNA transfection and adding of NF-κB pathway blocker (n = 20). The phosphorylation level of p65 protein in T lymphocytes increased greatly in AMI patients. Then, T lymphocytes were transfected by positive CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min. In addition, the positive plasmid transfection in T lymphocytes and Bay-11-7082 reduced the expression level both in the normal and AMI groups. * p < 0.05 vs. Normal group; Δp < 0.05 vs. AMI group.
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ijms-17-01397-f004: Expression of P-p65 in the T lymphocytes after CaSR siRNA transfection and adding of NF-κB pathway blocker (n = 20). The phosphorylation level of p65 protein in T lymphocytes increased greatly in AMI patients. Then, T lymphocytes were transfected by positive CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min. In addition, the positive plasmid transfection in T lymphocytes and Bay-11-7082 reduced the expression level both in the normal and AMI groups. * p < 0.05 vs. Normal group; Δp < 0.05 vs. AMI group.

Mentions: P65 is a subunit of NF-κB, which is a dimmer of members of the Rel proteins family. Activities of NF-κB intracellular signaling proteins often result in the activation of immuno-responsive cells, and the subsequent enhanced production of cytokines [12]. Our results showed that the phosphorylation level of p65 protein in T lymphocytes increased greatly in AMI patients compared with the normal controls. However, the CaSR-positive plasmid transfection in T lymphocytes reduced the expression level both in the normal and AMI groups. The NF-κB pathway blocker Bay-11-7082 had the same effect as positive CaSR siRNA transfection (p < 0.05) (Figure 4).


Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF- κ B Signaling Pathway
Expression of P-p65 in the T lymphocytes after CaSR siRNA transfection and adding of NF-κB pathway blocker (n = 20). The phosphorylation level of p65 protein in T lymphocytes increased greatly in AMI patients. Then, T lymphocytes were transfected by positive CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min. In addition, the positive plasmid transfection in T lymphocytes and Bay-11-7082 reduced the expression level both in the normal and AMI groups. * p < 0.05 vs. Normal group; Δp < 0.05 vs. AMI group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037677&req=5

ijms-17-01397-f004: Expression of P-p65 in the T lymphocytes after CaSR siRNA transfection and adding of NF-κB pathway blocker (n = 20). The phosphorylation level of p65 protein in T lymphocytes increased greatly in AMI patients. Then, T lymphocytes were transfected by positive CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min. In addition, the positive plasmid transfection in T lymphocytes and Bay-11-7082 reduced the expression level both in the normal and AMI groups. * p < 0.05 vs. Normal group; Δp < 0.05 vs. AMI group.
Mentions: P65 is a subunit of NF-κB, which is a dimmer of members of the Rel proteins family. Activities of NF-κB intracellular signaling proteins often result in the activation of immuno-responsive cells, and the subsequent enhanced production of cytokines [12]. Our results showed that the phosphorylation level of p65 protein in T lymphocytes increased greatly in AMI patients compared with the normal controls. However, the CaSR-positive plasmid transfection in T lymphocytes reduced the expression level both in the normal and AMI groups. The NF-κB pathway blocker Bay-11-7082 had the same effect as positive CaSR siRNA transfection (p < 0.05) (Figure 4).

View Article: PubMed Central - PubMed

ABSTRACT

Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear. In this study, we collected human peripheral blood T lymphocytes from patients with AMI and in different stages of percutaneous coronary intervention (PCI) (at the onset of AMI, the first day after PCI (PCI-1), PCI-3, and PCI-5) to study the CaSR and NF-&kappa;B pathway protein expression, cytokine release and T cell apoptosis. The results showed that the expressions of CaSR, P-p65, Caspase-12, and the secretions of Th-1 and Th-2 type cytokines were increased at the onset of AMI, especially on the PCI-1. Meanwhile, the apoptosis rate of CD3+, CD4+ and CD8+ T lymphocytes also increased. However, from PCI-3, all the indicators began to decline. In addition, we also found that positive CaSR small interfering RNA (siRNA) transfection in T lymphocytes and NF-&kappa;B pathway blocker Bay-11-7082 reversed the increased expressions of CaSR, P-p65, Caspase-12, reduced the secretions of Th-1 and Th-2 type cytokines, and decreased T lymphocytes apoptosis rate not only in the AMI patients but also in the normal controls. All of these results indicated that CaSR in the human peripheral blood T lymphocytes were involved in the AMI onset and progression, which probably was related to the NF-&kappa;B pathway. Our study demonstrated the relationship between AMI and CaSR, and will provide new effective prevention theory and new targets for drug treatment.

No MeSH data available.