Expression of the calcium sensing receptor in human peripheral blood T lymphocyte and its contribution to cytokine secretion through MAPKs or NF-κB pathways

Mol Immunol. 2013 Apr;53(4):414-20. doi: 10.1016/j.molimm.2012.09.010. Epub 2012 Oct 24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / pharmacology
  • Calcium / metabolism
  • Cells, Cultured
  • Gadolinium / pharmacology
  • Gene Expression Regulation* / drug effects
  • Humans
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Lymphotoxin-alpha / immunology
  • Lymphotoxin-alpha / metabolism*
  • MAP Kinase Kinase 4 / antagonists & inhibitors
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nitriles / pharmacology
  • Phosphorylation
  • Quinoxalines / pharmacology
  • Receptors, Calcium-Sensing / agonists
  • Receptors, Calcium-Sensing / antagonists & inhibitors
  • Receptors, Calcium-Sensing / genetics*
  • Receptors, Calcium-Sensing / metabolism
  • Signal Transduction
  • Sulfones / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transcription Factor RelA / antagonists & inhibitors
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 2-quinoxaline-carboxamide-N-adamantan-1-yl
  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • CASR protein, human
  • Interleukin-6
  • Lymphotoxin-alpha
  • Nitriles
  • Quinoxalines
  • Receptors, Calcium-Sensing
  • Sulfones
  • Transcription Factor RelA
  • Gadolinium
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • gadolinium chloride
  • Adamantane
  • Calcium