The Role Of Calcium-sensing Receptor In Human Peripheral T Lymphocytes And Related NF-κB And MAPK Signaling Pathways

Objective To observe the expression of calcium-sensing receptor (CaSR)on peripheral blood T lymphocytes of healthy adults and coronaryatherosclerotic heart disease (CAD) patients, the secretion of cytokineIL-6and TNF-β and the relation with NF-κB and MAPK signal transductionpathways.Methods Human peripheral T lymphocytes were isolated and cultured invitro with the PHA for activation; The expression of CaSR and signaltransduction related proteins in human T lymphocytes were identified byWestern blotting; The secretion of cytokines IL-6and TNF-β was analyzedby ELISA.Results CaSR protein expression increased in the peripheral blood Tlymphocytes in CAD patients and in normal human induced by CaSR agonist.CaSR agonist promoted signaling pathways proteins P-65and P-ERKexpression, which was reversed by the NF-κB and MAPK pathway inhibitors.But, P-JNK and P-38have no significant changes; The secretion of IL-6and TNF-β was higher than normal human in CAD patients, and CaSRactivation induced normal human T lymphocytes to secret more cytokinesIL-6and TNF-β. But, these effects could be inhibited by NF-κB and MAPKpathway inhibitors and partly by CaSR inhibitors NPS2390.Conclusion CaSR agonist promoted CaSR protein expression in theperipheral blood T lymphocytes; CaSR activation promoted the secretionof cytokines IL-6and TNF-β probably through NF-κB and ERK1/2signaltransduction pathways; CaSR expression in the peripheral blood Tlymphocytes and the secretion of cytokines IL-6and TNF-β increased inCAD patients, which may be related with NF-κB and MAPK signalingpathways.