Calcium-sensing receptors in human peripheral T lymphocytes and AMI: Cause and effect

Abstract

Acute myocardial infarction (AMI) is a disease associated with inflammation. T lymphocytes are involved by secreting cytokines and inflammatory factors. In our previous study, it was found that the T lymphocytes exhibited certain functional changes, the onset of which was induced by modulating calcium-sensing receptor (CaSR) in AMI. In the present study, western blotting was used to verified the expression of T lymphocyte CaSR and pathway proteins, including phosphorylated extracellular signal-regulated kinase (P-ERK)1/2 and phosphorylated c-Jun N-terminal kinase (P-JNK), and used cytometric bead array to detect the secretion of interleukin (IL)-4, IL-6, IL-10 and tumor necrosis factor (TNF)-α in AMI onset, the results demonstrated that they were all increased. In addition, the expression of T lymphocyte pathway proteins, including P-ERK1/2 and P-JNK, and the secretion of IL-4, IL-6, IL-10 and TNF-α decreased after T lymphocytes being transfected by CaSR small interfering RNA. By contrast, the neonatal mouse cardiomyocytes under hypoxia and hypoxia/re-oxygenation exhibited ultrastructural damage, increased apoptosis, increased production of lactate dehydrogenase (LDH) and malondialdehyde, and reduced superoxide dismutase; these indicators changed extensively when cardiomyocytes were co-cultured with T lymphocytes. However, the effects were reversed when the cardiomyocytes were co-cultured with CaSR-silenced T lymphocytes. These results indicated that CaSR may modulate T lymphocytes to release cytokines through mitogen-activated protein kinase pathways and affect cardiomyocyte injury. The relationship between AMI and T lymphocyte CaSR is reciprocal.