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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adamantane / analogs & derivatives
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Adamantane / pharmacology
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Calcium / metabolism
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Cells, Cultured
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Gadolinium / pharmacology
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Gene Expression Regulation* / drug effects
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Humans
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Interleukin-6 / immunology
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Interleukin-6 / metabolism*
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Lymphotoxin-alpha / immunology
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Lymphotoxin-alpha / metabolism*
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MAP Kinase Kinase 4 / antagonists & inhibitors
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MAP Kinase Kinase 4 / genetics
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MAP Kinase Kinase 4 / metabolism
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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Nitriles / pharmacology
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Phosphorylation
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Quinoxalines / pharmacology
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Receptors, Calcium-Sensing / agonists
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Receptors, Calcium-Sensing / antagonists & inhibitors
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Receptors, Calcium-Sensing / genetics*
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Receptors, Calcium-Sensing / metabolism
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Signal Transduction
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Sulfones / pharmacology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Transcription Factor RelA / antagonists & inhibitors
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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2-quinoxaline-carboxamide-N-adamantan-1-yl
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3-(4-methylphenylsulfonyl)-2-propenenitrile
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CASR protein, human
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Interleukin-6
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Lymphotoxin-alpha
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Nitriles
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Quinoxalines
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Receptors, Calcium-Sensing
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Sulfones
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Transcription Factor RelA
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Gadolinium
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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gadolinium chloride
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Adamantane
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Calcium