bay-11-7082 and gadolinium-chloride

The calcium-sensing receptor (CaSR) has been reported to play an important role in many tissues and organs. However, studies about the expression and function of CaSR in T lymphocytes are still not very lucid. In this study, we investigated the above-mentioned issues using RT-PCR, immunofluorescence staining, Western blotting, and the ELISA techniques. We found that the CaSR protein was expressed, and mainly located in the membrane in the normal human peripheral blood T lymphocytes. GdCl(3) (an agonist of CaSR) increased the dose-dependency of the CaSR expression, which was abolished by NPS2390 (an inhibitor of CaSR). GdCl(3) and Ca(2+) increased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 (one subgroup of MAPKs) and P65 (subunit of NF-κB),but, they had no significant effects on the JNK and P38 subgroups of MAPKs. Meantime, GdCl(3) and Ca(2+) stimulated both the IL-6 and TNF-β releases and their mRNA expressions. However, these effects of GdCl(3) and Ca(2+) were inhibited by NPS2390, U0126 (MAPKs pathway inhibitor) or Bay-11-7082 (NF-κB pathway inhibitor). These results suggested that CaSR was functionally expressed in the T cells, and the activated CaSR contributed to the cytokine secretion through the partial MAPK and NF-κB pathways.

Topics: Adamantane; Calcium; Cells, Cultured; Gadolinium; Gene Expression Regulation; Humans; Interleukin-6; Lymphotoxin-alpha; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitriles; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Quinoxalines; Receptors, Calcium-Sensing; Signal Transduction; Sulfones; T-Lymphocytes; Transcription Factor RelA