PMID- 24043258
OWN - NLM
STAT- MEDLINE
DCOM- 20140130
LR  - 20211021
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 305
IP  - 11
DP  - 2013 Dec 1
TI  - Cell matrix contact modifies endothelial major histocompatibility complex class 
      II expression in high-glucose environment.
PG  - H1592-9
LID - 10.1152/ajpheart.00018.2013 [doi]
AB  - Atherosclerosis is a chronic inflammatory disease. Cardiovascular risk factors 
      such as hyperglycemia, hyperlipidemia, and arterial hypertension induce 
      endothelial dysfunction with alterations in endothelial biosecretion and immune 
      behavior. The aim of this study is to elucidate whether glucose-induced 
      modifications of endothelial biosecretory and immune functions are regulated by 
      interactions of endothelial cells (ECs) with their extracellular matrix [ECs 
      plated on polystyrene-coated tissue culture plates (TC-EC) vs. ECs embedded 
      within three-dimensional (3-D) collagen-based matrixes (3D-EC)]. In the absence 
      of glucose, IFN-gamma-induced phosphorylation of JAK and STAT proteins and human 
      leukocyte antigen (HLA)-DR expression were lower in 3D-EC compared with TC-EC. 
      Inversely, the expression of suppressor of cytokine signaling proteins (SOCS)-1 
      and -3 were significantly higher in naive 3D-EC compared with naive TC-EC. 
      IFN-gamma-induced upregulation of SOCS proteins was further amplified by the 3-D 
      environment. Glucose significantly augmented IFN-gamma-dependent signaling pathways 
      in TC-EC. IFN-gamma-induced phosphorylation of JAK and STAT proteins as well as 
      HLA-DR expression by ECs in low- and high-glucose medium was significantly lower 
      in 3-D than in two-dimensional environment. Glucose increased SOCS expression in 
      TC-EC and 3D-EC to the same extent, such that expression levels in 3D-EC exceeded 
      SOCS-1 and -3 expression in TC-EC by 1.6-2.5-fold. In conclusion, low- and 
      high-glucose concentrations amplify IFN-gamma-induced signaling pathways in TC-EC. 
      Increased SOCS expression raises the threshold for IFN-gamma to induce HLA-DR 
      expression in a 3-D environment. This immunoprotective effect is maintained even 
      in states of experimental hyperglycemia.
FAU - Nickmann, Markus
AU  - Nickmann M
AD  - Department of Internal Medicine/Cardiology, University Hospital Grosshadern, 
      Ludwig-Maximilians University, Munich, Germany;
FAU - Saemisch, Michael
AU  - Saemisch M
FAU - Wilbert-Lampen, Ute
AU  - Wilbert-Lampen U
FAU - Nickel, Thomas
AU  - Nickel T
FAU - Edelman, Elazer R
AU  - Edelman ER
FAU - Methe, Heiko
AU  - Methe H
LA  - eng
GR  - R01 GM049039/GM/NIGMS NIH HHS/United States
GR  - R01-GM-49039/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130916
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Collagen Type IV)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (SOCS1 protein, human)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.10.2 (Janus Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Proliferation
MH  - Cell-Matrix Junctions/immunology/*metabolism
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Collagen Type IV/*metabolism
MH  - Endothelial Cells/immunology/*metabolism
MH  - Gelatin Sponge, Absorbable
MH  - Glucose/*metabolism
MH  - HLA-DR Antigens/*metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Janus Kinases/metabolism
MH  - Lymphocyte Activation
MH  - Phosphorylation
MH  - STAT Transcription Factors/metabolism
MH  - Signal Transduction
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/metabolism
MH  - T-Lymphocytes/immunology/metabolism
MH  - Time Factors
PMC - PMC3882461
OTO - NOTNLM
OT  - ECM
OT  - diabetes
OT  - endothelial cell
OT  - immunomodulation
EDAT- 2013/09/18 06:00
MHDA- 2014/01/31 06:00
PMCR- 2014/12/01
CRDT- 2013/09/18 06:00
PHST- 2013/09/18 06:00 [entrez]
PHST- 2013/09/18 06:00 [pubmed]
PHST- 2014/01/31 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - ajpheart.00018.2013 [pii]
AID - H-00018-2013 [pii]
AID - 10.1152/ajpheart.00018.2013 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2013 Dec 1;305(11):H1592-9. doi: 
      10.1152/ajpheart.00018.2013. Epub 2013 Sep 16.