PMID- 30575933
OWN - NLM
STAT- MEDLINE
DCOM- 20200113
LR  - 20200113
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 22
IP  - 24
DP  - 2018 Dec
TI  - ICOS/ICOSL upregulation mediates inflammatory response and endothelial 
      dysfunction in type 2 diabetes mellitus.
PG  - 8898-8908
LID - 16659 [pii]
LID - 10.26355/eurrev_201812_16659 [doi]
AB  - OBJECTIVE: ICOS/ICOSL plays a crucial part in various disease-mediated immune 
      responses. However, the exact role of ICOS/ICOSL in type 2 diabetes mellitus 
      (T2DM) development remains unexplored. This study aims to investigate the role of 
      ICOS/ICOSL in the pathogenesis of T2DM. MATERIALS AND METHODS: Human peripheral 
      blood T-lymphocytes (CD3) and umbilical vein endothelial cells (HUVECs) were 
      treated with high-glucose (HG) or advanced glycation end products (AGEs). A 
      portion of CD3 cells was co-cultured with HUVECs and treated with different 
      mediums or anti-ICOS mAbs. The ICOS/ICOSL and caspase-3 protein expression was 
      measured by Western blotting. ELISA (enzyme-linked immunosorbent assay), MTT 
      (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and NOx 
      production assays were respectively used to detect cytokines level, cell 
      viability and the production of NOx. RESULTS: HG and AGEs significantly 
      upregulated ICOS/ICOSL expressions in T cells and HUVECs. T cell contact with 
      HUVECs secreted more IFN-gamma, IL-4, and IL-10 compared to non-contact cells, while 
      cytokines from IL-6-, IL-1beta-, and CM- (the conditioned medium) treated cells did 
      not differ from the control. A significant increase of IL-8 and IL-6 was found in 
      HUVECs under both contact and non-contact conditions vs. control cells. Similar 
      results were also observed in the comparison between CM1- (T cell condition 
      medium) or CM2- (co-culture condition medium) treated cells and control cells. 
      However, CM1 and CM2 treatment significantly inhibited cell viability and 
      increased caspase-3 and NOx production; blocking ICOS/ICOSL remarkably decreased 
      cytokines secretion, enhanced cell viability and reduced caspase-3 and NOx 
      production. CONCLUSIONS: HG and AGEs cause T cell inflammatory response and 
      vascular endothelial dysfunction by upregulating ICOS/ICOSL, which may be one of 
      the possible mechanisms of cardiovascular complications development in T2DM 
      patients.
FAU - Zhang, H-Y
AU  - Zhang HY
AD  - Department of Geriatrics, the First People's Hospital of Yunnan Province, the 
      Affiliated Hospital of Kunming University of Science and Technology, Kunming, 
      Yunnan Province, China. rou3726@163.com.
FAU - Ruan, L-B
AU  - Ruan LB
FAU - Li, Y
AU  - Li Y
FAU - Yang, T-R
AU  - Yang TR
FAU - Liu, W-J
AU  - Liu WJ
FAU - Jiang, Y-X
AU  - Jiang YX
FAU - Li, T-R
AU  - Li TR
FAU - Quan, J
AU  - Quan J
FAU - Xuan, W
AU  - Xuan W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (CD3 Complex)
RN  - 0 (Cytokines)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (ICOS protein, human)
RN  - 0 (ICOSLG protein, human)
RN  - 0 (Inducible T-Cell Co-Stimulator Ligand)
RN  - 0 (Inducible T-Cell Co-Stimulator Protein)
RN  - 0 (Inflammation Mediators)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - CD3 Complex/metabolism
MH  - Cell Communication
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/immunology/*metabolism
MH  - Diabetes Mellitus, Type 2/blood/immunology/*metabolism
MH  - Endothelium, Vascular/drug effects/immunology/*metabolism
MH  - Glucose/toxicity
MH  - Glycation End Products, Advanced/toxicity
MH  - Human Umbilical Vein Endothelial Cells/drug effects/immunology/*metabolism
MH  - Humans
MH  - Inducible T-Cell Co-Stimulator Ligand/immunology/*metabolism
MH  - Inducible T-Cell Co-Stimulator Protein/immunology/*metabolism
MH  - Inflammation Mediators/immunology/*metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes/drug effects/immunology/*metabolism
EDAT- 2018/12/24 06:00
MHDA- 2020/01/14 06:00
CRDT- 2018/12/22 06:00
PHST- 2018/12/22 06:00 [entrez]
PHST- 2018/12/24 06:00 [pubmed]
PHST- 2020/01/14 06:00 [medline]
AID - 16659 [pii]
AID - 10.26355/eurrev_201812_16659 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8898-8908. doi: 
      10.26355/eurrev_201812_16659.