title: Calcium-sensing receptor in the T lymphocyte enhanced the apoptosis and cytokine secretion in sepsis.
abstract: Calcium-sensing receptor (CaSR) is a member of the G protein-coupled receptor superfamily that existed in lymphocytes and promoted cytokine secretion. Lymphocytes are also involved in sepsis. However, the role of CaSR in lymphocytes in sepsis is unclear. In this study, we want to examine whether the CaSR in lymphocytes in sepsis is involved in the cytokine secretions and apoptosis and make clear the relationship between NF-κB and MAPK signal transduction pathways. We investigated the issues mentioned earlier using Western blotting, ELISA, and Flow Cytometry. The sepsis was remodeled by cecal ligation and puncture (CLP). We found that CaSR protein expression increased in the peripheral blood T lymphocytes in CLP rats. The calcimimetic R568 (NPS R568) promoted, whereas the calcilytic NPS 2143 attenuated, signaling pathways proteins P65 (subunit of NF-κB), ERK1/2, and JNK (one subgroup of MAPKs) phosphorylation. However, P-P38 and P-JAKs exhibit no significant changes. Furthermore, the production TNF-α and IL-4 was greater in CLP rats than in normal rats, and NPS R568 promoted secretion of these cytokines. Simultaneously, the apoptotic ratio of T cells in CLP increased, and NPS R 568 exacerbated the apoptosis degree. However, these effects could also be inhibited by U0126 or SP600125 (MAPKs pathway inhibitor) or Bay-11-7082 or (NF-κB pathway inhibitor). From these results, we can conclude that, in the sepsis, CaSR activation promoted T-cell apoptosis and the secretion of pro-inflammatory cytokine TNF-α and anti-inflammatory cytokines IL-4 probably through NF-κB and partial MAPK signal transduction pathways.
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Chun-li
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Qiu-yue
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Du
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jing-ya
authors.initials: JY
authors.lastname: Zeng
authors.affiliation: Department of Clinical Laboratory, Daqing Affiliated School of Harbin Medical University, Daqing 150000, China.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin 150086, China.
authors.forename: Chang-qing
authors.initials: CQ
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: syh200415@126.com.
authors.forename: Yi-hua
authors.initials: YH
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002432:Cecum / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D015847:Interleukin-4 / Q000378:metabolism*; D008026:Ligation; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011677:Punctures; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D044169:Receptors, Calcium-Sensing; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4
keywords: Calcium-sensing receptor; Cytokine; Lymphocyte; Sepsis; Signaling transduction pathway