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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.


The levels of cytokines in the different stages of AMI and PCI and changed by CaSR siRNA transfection and NF-κB pathway blocker (n = 20). The levels of Th-1 type and Th-2 type cytokines in the plasma and the supernatant of cultured T cells were detected by Cytometric Bead Array. (A,B) Showed that the plasma levels of cytokines in AMI onset and at the different stages of PCI; (C,D) show the Th-1 and Th-2 type cytokines concentration after T lymphocytes were transfected by CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min in the supernatant. * p < 0.05 vs. Normal; #p < 0.05 vs. AMI group; ▲p < 0.05 vs. PCI-1 group; ■p < 0.05 vs. PCI-3 group; □p < 0.05 vs. Normal + siRNA+; Δp < 0.05 vs. AMI; ◊p < 0.05 vs. AMI + siRNA+.
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ijms-17-01397-f005: The levels of cytokines in the different stages of AMI and PCI and changed by CaSR siRNA transfection and NF-κB pathway blocker (n = 20). The levels of Th-1 type and Th-2 type cytokines in the plasma and the supernatant of cultured T cells were detected by Cytometric Bead Array. (A,B) Showed that the plasma levels of cytokines in AMI onset and at the different stages of PCI; (C,D) show the Th-1 and Th-2 type cytokines concentration after T lymphocytes were transfected by CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min in the supernatant. * p < 0.05 vs. Normal; #p < 0.05 vs. AMI group; ▲p < 0.05 vs. PCI-1 group; ■p < 0.05 vs. PCI-3 group; □p < 0.05 vs. Normal + siRNA+; Δp < 0.05 vs. AMI; ◊p < 0.05 vs. AMI + siRNA+.

Mentions: According to the reports, in response to inflammation in patients with AMI, great deals of cytokines were involved, including Th-1 cytokines and Th-2 cytokines [16,17]. We also know that lymphocytes secrete cytokine to participate in the immunological reaction. In this part, we tested that the levels of both the Th-1 type cytokines and Th-2 type cytokines, such as IL-2, IFN-γ, TNF-α and IL-4, IL-6, IL-10, increased in the plasma at the AMI onset, climbed to the highest level at the PCI-1, and began to decrease from PCI-3. In PCI-5, Th-1 type cytokines dropped to the normal level, but the levels of Th-2 type cytokines were still slightly higher (Figure 5A,B).


Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF- κ B Signaling Pathway
The levels of cytokines in the different stages of AMI and PCI and changed by CaSR siRNA transfection and NF-κB pathway blocker (n = 20). The levels of Th-1 type and Th-2 type cytokines in the plasma and the supernatant of cultured T cells were detected by Cytometric Bead Array. (A,B) Showed that the plasma levels of cytokines in AMI onset and at the different stages of PCI; (C,D) show the Th-1 and Th-2 type cytokines concentration after T lymphocytes were transfected by CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min in the supernatant. * p < 0.05 vs. Normal; #p < 0.05 vs. AMI group; ▲p < 0.05 vs. PCI-1 group; ■p < 0.05 vs. PCI-3 group; □p < 0.05 vs. Normal + siRNA+; Δp < 0.05 vs. AMI; ◊p < 0.05 vs. AMI + siRNA+.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037677&req=5

ijms-17-01397-f005: The levels of cytokines in the different stages of AMI and PCI and changed by CaSR siRNA transfection and NF-κB pathway blocker (n = 20). The levels of Th-1 type and Th-2 type cytokines in the plasma and the supernatant of cultured T cells were detected by Cytometric Bead Array. (A,B) Showed that the plasma levels of cytokines in AMI onset and at the different stages of PCI; (C,D) show the Th-1 and Th-2 type cytokines concentration after T lymphocytes were transfected by CaSR siRNA plasmid for 24 h or cultured by NF-κB pathway blocker Bay-11-7082 (10 mM) for 15 min in the supernatant. * p < 0.05 vs. Normal; #p < 0.05 vs. AMI group; ▲p < 0.05 vs. PCI-1 group; ■p < 0.05 vs. PCI-3 group; □p < 0.05 vs. Normal + siRNA+; Δp < 0.05 vs. AMI; ◊p < 0.05 vs. AMI + siRNA+.
Mentions: According to the reports, in response to inflammation in patients with AMI, great deals of cytokines were involved, including Th-1 cytokines and Th-2 cytokines [16,17]. We also know that lymphocytes secrete cytokine to participate in the immunological reaction. In this part, we tested that the levels of both the Th-1 type cytokines and Th-2 type cytokines, such as IL-2, IFN-γ, TNF-α and IL-4, IL-6, IL-10, increased in the plasma at the AMI onset, climbed to the highest level at the PCI-1, and began to decrease from PCI-3. In PCI-5, Th-1 type cytokines dropped to the normal level, but the levels of Th-2 type cytokines were still slightly higher (Figure 5A,B).

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.