title: Expression of the calcium sensing receptor in human peripheral blood T lymphocyte and its contribution to cytokine secretion through MAPKs or NF-κB pathways.
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.
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Mingrui
authors.initials: M
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Yin
authors.forename: Chunli
authors.initials: C
authors.lastname: Wu
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Wu
authors.forename: Shanli
authors.initials: S
authors.lastname: Feng
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Luan
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.forename: Lixin
authors.initials: L
authors.lastname: Yan
authors.forename: Binhui
authors.initials: B
authors.lastname: Zhao
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005682:Gadolinium / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000276:immunology / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011810:Quinoxalines / Q000494:pharmacology; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C569355:2-quinoxaline-carboxamide-N-adamantan-1-yl; C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C095550:CASR protein, human; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D009570:Nitriles; D011810:Quinoxalines; D044169:Receptors, Calcium-Sensing; D013450:Sulfones; D051996:Transcription Factor RelA; D005682:Gadolinium; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C038958:gadolinium chloride; D000218:Adamantane; D002118:Calcium