PMID- 30268079
OWN - NLM
STAT- MEDLINE
DCOM- 20190501
LR  - 20190501
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 103
DP  - 2018 Nov
TI  - CD8+iTregs attenuate glomerular endothelial cell injury in lupus-prone mice 
      through blocking the activation of p38 MAPK and NF-kappaB.
PG  - 133-143
LID - S0161-5890(18)30769-7 [pii]
LID - 10.1016/j.molimm.2018.09.006 [doi]
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory disease. Endothelial 
      cell injury plays an important role in the inflammatory processes associated with 
      SLE. CD4+Foxp3+regulatory T cells (Tregs) reduce the injury to endothelial cells 
      induced by inflammatory factors. As a newly identified regulatory T cell, we 
      previously reported that CD8+CD103+iTregs had similar effects to those of 
      CD4+iTregs in the process of immunoregulation. In this paper, we further explored 
      the effect and mechanism of CD8+iTregs on endothelial cell injury. The 
      expressions of vascular cellular adhesion molecule-1 (VCAM-1), intracellular 
      adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha 
      (TNF-alpha), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in 
      MRL/lpr mouse glomerular endothelial cells (lupus-MGECs) were estimated by 
      quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent 
      assay and Western blotting. The lupus-MGEC apoptosis rate was detected by flow 
      cytometry and the adhesion of monocyte-like cells to lupus-MGECs exposed to 
      lipopolysaccharide (LPS) was determined by the adhesion assay. Additionally, the 
      expressions of P-p38, P-NF-kappaB and P-IkappaBalpha were detected by Western blotting. The 
      results showed that LPS increased the expressions of VCAM-1, ICAM-1, IFN-gamma, 
      TNF-alpha, IL-6 and MCP-1 in lupus-MGECs, while CD8+iTregs significantly decreased 
      the levels of these adhesion molecules and inflammatory mediators. Furthermore, 
      CD8+iTregs alleviated lupus-MGEC apoptosis and inhibited the adhesion of 
      monocyte-like cells to lupus-MGECs. Both nuclear factor-kappaB (NF-kappaB) and p38 
      mitogen-activated protein kinase (MAPK), activated by LPS, were suppressed by 
      CD8+iTregs. These findings suggest that CD8+iTregs attenuate LPS-induced 
      glomerular endothelial cell injury through blocking the activation of p38 MAPK 
      and NF-kappaB in lupus-MGECs. The protective effect of CD8+iTregs indicates their 
      possible therapeutic application in Lupus nephritis.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Liu, Ya
AU  - Liu Y
AD  - Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, China.
FAU - Deng, Weijuan
AU  - Deng W
AD  - Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, China.
FAU - Meng, Qiaoyun
AU  - Meng Q
AD  - Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, China.
FAU - Qiu, Xiaonan
AU  - Qiu X
AD  - Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, China.
FAU - Sun, Dong
AU  - Sun D
AD  - Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, China. Electronic address: 767946775@qq.com.
FAU - Dai, Chun
AU  - Dai C
AD  - Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, China. Electronic address: 13615133736@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180927
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
EIN - Mol Immunol. 2019 Jul;111:220. PMID: 31174855
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism
MH  - Cell Adhesion Molecules/genetics/metabolism
MH  - Cells, Cultured
MH  - Endothelial Cells/drug effects/*immunology/metabolism
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Inflammation Mediators/immunology/metabolism
MH  - Kidney Glomerulus/cytology
MH  - Lipopolysaccharides/pharmacology
MH  - Lupus Erythematosus, Systemic/genetics/*immunology/metabolism
MH  - Mice, Inbred MRL lpr
MH  - NF-kappa B/*immunology/metabolism
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism
MH  - U937 Cells
MH  - p38 Mitogen-Activated Protein Kinases/*immunology/metabolism
OTO - NOTNLM
OT  - CD8+iTregs
OT  - Glomerular endothelial cell
OT  - Inflammatory mediators
OT  - Lupus nephritis
OT  - Monocyte adhesion
EDAT- 2018/09/30 06:00
MHDA- 2019/05/02 06:00
CRDT- 2018/09/30 06:00
PHST- 2018/04/26 00:00 [received]
PHST- 2018/09/01 00:00 [revised]
PHST- 2018/09/09 00:00 [accepted]
PHST- 2018/09/30 06:00 [pubmed]
PHST- 2019/05/02 06:00 [medline]
PHST- 2018/09/30 06:00 [entrez]
AID - S0161-5890(18)30769-7 [pii]
AID - 10.1016/j.molimm.2018.09.006 [doi]
PST - ppublish
SO  - Mol Immunol. 2018 Nov;103:133-143. doi: 10.1016/j.molimm.2018.09.006. Epub 2018 
      Sep 27.